Avril V. Somlyo, Ph.D.

Avril V. Somlyo, Ph.D.

Avril V. Somlyo, Ph.D.                                                                                

Graduate School:University of Pennsylvania                                                                 Primary Appointment: Professor of Molecular Physiology and Biological Physics

 

E-mail
Address:
avs5u@virginia.edu
Telephone: 434-982-0825
Address: Molecular Physiology
and Biological Physics
University of Virginia
PO Box 800736
Charlottesville, VA 22908-0736

somlyo,av

 


Research Description

The molecular mechanisms of excitation-contraction coupling, contractile regulation and the basis of contraction in mammalian smooth and cardiac muscle  in normal and pathological states are long-term interests of our laboratory. We are currently working on a signal transduction pathway in smooth muscle, which is activated when physiological transmitters or drugs bind to cell membrane receptors and lead to a marked increase in the sensitivity of the contractile proteins to calcium (Ca2+-sensitization). We have found that this G-protein-coupled process, which operates under physiological conditions, inhibits myosin light chain phosphatase, resulting in an increased population of phosphorylated (activated), cycling myosin motors. The phosphatase is a trimeric complex with a 130 kDa subunit which targets the activity to myosin. Current biochemical and molecular biological studies are directed to establishing the messengers between the membrane receptors/G-proteins and the myosin-associated phosphatase, as well as elucidating the mechanism of inhibition of the enzyme. The small G-protein RhoA and Rho-kinase, which can phosphorylate and inhibit myosin phosphatase, participate in this signaling cascade in muscle and non-muscle cells. This same pathway modulates cell migration, and we are exploring its role in angiogenesis and in tumor cell metastasis. Rho signaling likely plays a role in the migration of smooth muscle cells during post-angioplasty restenosis. Biochemical and molecular biological techniques and physiological studies of permeabilized smooth muscle cells are used to identify the signaling molecules and their targets, as well as cross-talk among various other signaling pathways. Photolysis of caged compounds are used to determine the kinetics of various steps in these signaling cascades.

Transgenic and knockout mice are used to elucidate the role of telokin, a molecule found in small–but not large–blood vessels. We have found that telokin is phosphorylated upon cyclic nucleotide-induced relaxation. Recombinant telokin added back to telokin-depleted muscles produces a profound relaxation and dephosphorylation of myosin light chains. We are testing the hypothesis that it functions by activating myosin phosphatase. A myosin light chain kinase deletion mouse, embryonic lethal at 14 days P.C., is under study to determine the role of MLCK in the development of the vasculature and heart.

Fig: Smooth muscle myosin molecules imaged by cryoatomic force microscopy (in collaboration with Dr. Zhifeng Shao's laboratory) showing the 2 heads with associated light chains and the coiled-coil tail.

Another focus in our laboratory is the mapping of subcellular calcium distribution and handling in cardiac muscle during physiological stimuli and calcium overload. Electron probe X-ray microanalysis is used to determine and image, at high spatial resolution, elemental distributions within cardiac muscle organelles and membranes. Intracellular chloride accumulation and subcellular elemental distribution were determined by in situ freezing of atria during atrial fibrillation. We are particularly interested in the affinity of mitochondria for calcium during normal systole and diastole and in the role of calcium binding to intercalated disks and gap junctions during cardiac arrhythmias. We are currently studying the role of Ca binding to cadherins at intercalated disks which we propose to be a specialized compartment involved in abnormal conduction.

Contraction in smooth muscle, mediated by interactions between actin filaments and crossbridges on adjacent myosin filaments, is triggered by the rise in cytoplasmic calcium and consequent phosphorylation of the 20 kDa light chains of myosin. The crossbridges are the motors that utilize ATP as an energy source for the generation of force and work. The kinetics of this motor and its modulation in muscle are characterized in our laboratory by using photolysis of caged nucleotides, caged Ca2+ and caged Bapta and monitoring force and stiffness transients. We use a new, fluorescently labeled, genetically engineered mutant of a bacterial phosphate-binding protein or a fluorescent MgADP to follow the kinetic relationship between force development and phosphate or ADP release respectively from the ATP binding pocket of the crossbridge following photolysis of caged ATP. The rationale for studying crossbridge kinetics in permeabilized fibers, rather than in solutions of purified proteins, is that the biological ATPase cycle is modulated by the physical strain on the crossbridges. Current efforts are toward determining the role of strain and phosphorylation on ADP affinity and its potential role in the maintenance of high force at low ATPase activity, a characteristic of the high economy of energy usage by smooth muscle. Our goal for these studies is to understand the fundamental properties of the crossbridge motors, their differences and their regulation in fast and in slowly contracting smooth muscles.

The long-term aim of our work is to provide insights into the abnormalities of disease states involving smooth muscle, such as hypertension, post angioplasty restenosis, coronary artery disease, angiogenesis and asthma.

Techniques in Use Laser flash photolysis of caged compounds, electron microscopy, X-ray microprobe analysis, confocal microscopy, permeabilized cell assays, biochemical methods for the isolation and identification of signaling molecules, recombinant protein production, 2-hybrid screens, RNA interference.


Selected Publications:

 Legend: Confocal image of gastrointestinal smooth muscle cells of the ileum into which fluorescent heparin, a blocker of inositol trisphosphate Ca2+-release, has been introduced by a reversible permeabilization protocol in order to evaluate the role of this pathway in agonist-induced contractions of intact muscle. Fluorescent heparin is seen in the cytoplasm of the cells as well as bound to the nuclei.

Somlyo, AV and Siegman M (2011) Smooth Muscle-Myocyte Ultrastructure and Contractility In: Muscle: Fundamental Biology and Mechanisms of Disease. Eds. Joseph A. Hill, MD, PhD, and Eric N Olson, Ph.D. (In Press)

Hoofnagle MH, Neppl RL, Berzin EL, Pipes GC, Olson EN, Wamhoff BW, Somlyo AV, Owens GK. Myocardin is Differentially Required for the Development of Smooth Muscle Cells and Cardiomyocytes. Am J Physiol Heart Circ Physiol. 2011 Feb 25:300:H1707-H1721 [Epub ahead of print] PMID: 21357509

Zieba BJ, Artamonov MV, Jin L, Momotani K, Ho R, Franke AS, Neppl RL, Stevenson AS, Khromov AS, Somlyo AV. (2011) The cAMP responsive Rap1 guanine nucleotide exchange factor, Epac, induces smooth muscle relaxation by down regulation of RhoA activity. J. Biol. Chem. 286:16681-16692 PMID: 2145456/PMCID: PMC3089510 (Available on 2012/5/13)

Jin L, Gan Q, Zieba BJ, Goicoechea SM, Owens GK, Otey CA, Somlyo AV. (2010) The actin associated protein palladin is important for the early smooth muscle cell differentiation.  PLoS One. 2010 Sep 22;5(9):e12823  PMCID: PMC2943901

Hoofnagle MH, Neppl RL. Pipes TGC, Olson EN, Wamhoff BW, Somlyo AV, Owens GK. Myocardin is Required for Normal Ventricular Myocyte Development in the Mouse  (In Revision)

Yoshida T, Gan Q, Franke AS, Ho R, Zhang j, Chen YE, Hayashi M, Majewsky MW. Somlyo AV, Owens GK. Smooth and cardiac muscle-selective knock-out of Kruppel- like factor 4 causes postnasal death and growth retardation. J Biol Chem. 2010 Jul 2:285(27):21175-84. Epub 2010 May 3. PMID:20439457

Khromov A, Choudhury N, Stevenson AS, Somlyo AV, Eto M. Phosphorylation-dependent autoinhibition of myosin light chain phosphatase accounts for Ca2+ sensitization force of smooth muscle contraction. J Biol Chem. 2009 Aug 7;284(32):21569-79. Epub 2009 Jun 15. PMID: 19531490

Zheng M, Cierpicki T, Momotani K, Artamonov MV, Derewenda U, Bushweller JH, Somlyo AV, Derewenda ZS. On the mechanism of autoinhibition of the RhoA-specific nucleotide exchange factor PDZRhoGEF. BMC Struct Biol. 2009 May 21;9:36. PMID: 19460155

Kim JI, Young GD, Jin L, Somlyo AV, Eto M. Expression of CPI-17 in smooth muscle during embryonic development and in neointimal lesion formation. Histochem Cell Biol. 2009 Aug;132(2):191-8. Epub 2009 May 13. PMID: 19437030

Jin L, Hastings NE, Blackman BR, Somlyo AV. Mechanical properties of the extracellular matrix alter expression of smooth muscle protein LPP and its partner palladin; relationship to early atherosclerosis and vascular injury.J Muscle Res Cell Motil. 2009;30(1-2):41-55. Epub 2009 Feb 10. PMID: 19205907

Neppl RL, Lubomirov LT, Momotani K, Pfitzer G, Eto M, Somlyo AV. Thromboxane A2-induced bi-directional regulation of cerebral arterial tone. J Biol Chem. 2009 Mar 6;284(10):6348-60. Epub 2008 Dec 17. PMID: 19095646

Jin L, Yoshida T, Ho R, Owens GK, Somlyo AV. The actin-associated protein Palladin is required for development of normal contractile properties of smooth muscle cells derived from embryoid bodies.J Biol Chem. 2009 Jan 23;284(4):2121-30. Epub 2008 Nov 17. PMID: 19015263

Wooldridge AA, Fortner CN, Lontay B, Akimoto T, Neppl RL, Facemire C, Datto MB, Kwon A, McCook E, Li P, Wang S, Thresher RJ, Miller SE, Perriard JC, Gavin TP, Hickner RC, Coffman TM, Somlyo AV, Yan Z, Haystead TA. Deletion of the protein kinase A/protein kinase G target SMTNL1 promotes an exercise-adapted phenotype in vascular smooth muscle. J Biol Chem. 2008 Apr 25;283(17):11850-9. Epub 2008 Feb 29. PMID: 18310078

Momotani K, Khromov AS, Miyake T, Stukenberg PT, Somlyo AV. Cep57, a multidomain protein with unique microtubule and centrosomal localization domains. Biochem J. 2008 Jun 1;412(2):265-73. PMID: 18294141

Feng J, Somlyo AP, Somlyo AV, Shao Z.J. Automated electron tomography with scanning transmission electron microscopy. Microsc. 2007 Dec;228(Pt 3):406-12. PMID: 18045335

Somlyo AV. Cyclic GMP regulation of myosin phosphatase: a new piece for the puzzle? Circ Res. 2007 Sep 28;101(7):645-7. PMID: 17901367

Li Jin, Michael J. Kern, Carol A. Otey, Brian R. Wamhoff, Avril V. Somlyo (2007) Angiotensin II, Focal Adhesion Kinase, and PRX1 Enhance Smooth Muscle Expression of Lipoma Preferred Partner and a Newly Identified Lipoma Preferred Partner Binding Partner Palladin to Promote Cell Migration. Circ Res [ View Entrez Listing]

Sinha, S., Wamhoff, B.R., Hoofnagle, M.H., Thomas, J., Neppl, R.L., Deering, T., Helmke, B., Bowles, D.K., Somlyo, A.V., and Owens, G.K. (2006) Assessment of Contractility of Purified Smooth Muscle Cells Derived from Embryonic Stem Cells. Stem Cells  [ View Entrez Listing]

Gorenne I., Yoshida T., Sanders J.M., Jin, L,  Sarembock  I.J., Owens G.K., Somlyo A.P., and Somlyo A.V.  (2006) LPP expression during in vitro smooth muscle differentiation and stent-induced vascular injury. Circ. Res. 98:378-385.  [ View Entrez Listing]


Khromov, A.S., H. Wang H., Choudhury N., McDuffie, M.J, Herring, P., Nakamoto, R., Owens, G.K., Somlyo, A.P, and Somlyo, A.V.   (2006) Smooth muscle of telokin deficient nice exhibits increased sensitivity to Ca2+ and decreased cGMP induced relaxation. Proc. Natl. Acad. Sci. 103:2440-2445. 
[ View Entrez Listing]

Choudhury N, Khromov AS, Somlyo AP, Somlyo AV.Telokin mediates Ca2+-desensitization through activation of myosin phosphatase in phasic and tonic smooth muscle. J Muscle Res Cell Motil. 2004;25(8):657-65. Epub 2005 Feb 24.  [ View Entrez Listing]

Somlyo AP, Somlyo AV.Signal transduction through the RhoA/Rho-kinase pathway in smooth muscle. J Muscle Res Cell Motil. 2004;25(8):613-5. No abstract available. 

Somlyo AV, Wang H, Choudhury N, Khromov AS, Majesky M, Owens GK, Somlyo AP.Myosin light chain kinase knockout. J Muscle Res Cell Motil. 2004;25(3):241-2. No abstract available.

Somlyo AV, Khromov AS, Webb MR, Ferenczi MA, Trentham DR, He ZH, Sheng S, Shao Z, Somlyo AP (2004)  Smooth muscle myosin: regulation and properties. Philos Trans R Soc Lond B Biol Sci. 2004 Dec 29;359(1452):1921-30. Review  [ View Entrez Listing]

Wamhoff, B.R., Bowles, D.K., McDonald, O.G., Sinha, S., Somlyo, A.P., Somlyo. A.V., and Owens, G.K. (2004) L-type voltage-gated Ca2+ channels modulate expression of smooth muscle differentiation marker genes via a Rho kinase/myocardin/SRF-dependent mechanism. Circ. Res. 95:406-414.  [ View Entrez Listing]


Perlegas, D. Xie. H., Sinha, S., Somlyo, A.V., and Owens, G.K. (2004) The Angiotensin II Type 2 Receptor Regulates Smooth Muscle Growth and Force Generation in Late Fetal Mouse Development.  Am J Physiol Heart Circ Physiol. 2005 Jan;288(1):H96-102. Epub 2004 Aug 26 .  [ View Entrez Listing]


Derewenda, U., Oleksy, A., Stevenson, A.S. Korczynska, J., Dauter, Z., Somlyo, A.P., Otlewski, J., Somlyo, A.V. and Derewenda, Z. (2004) The crystal structure of human RhoA in complex with the  DH/PH fragment of PDZRhoGEF, an activator of the Ca2+ sensitization pathway in smooth muscle.  Structure (Camb). 2004 Nov;12(11):1955-65 .  [ View Entrez Listing]


Stevenson, A.S., Matthew, J.D., Eto, M., Luo, S., Somlyo, A.P., and Somlyo, A.V. (2004) Uncoupling of GPCR and RhoA-induced Ca2+-sensitization of Chicken Amnion Smooth Muscle Lacking CPI-17.  FEBS Lett. 2004 Dec 3;578(1-2):73-9   [ View Entrez Listing]

Feng, J., Somlyo, A.V. and Somlyo A.P. (2004)  A system for acquiring simultaneous electron energy-loss and X-ray spectrum-images.  J. Microsc.  215:92-99 [View Entrez Listing]

Khromov, A.S., Webb, M.R., Ferenczi, M.A, Trentham, D.R., Somlyo, A.P., and Somlyo, A.V.(2004) Myosin regulatory light chain phosphorylation and strain modulate ADP-release from smooth muscle myosin. Biophy. J. 86:2318-2328 [View Entrez Listing]

Bonnevier, J., Fassler, R., Somlyo, A.P., Somlyo, A.V., and Arner, A. (2004)  Modulation of Ca2+ sensitivity by cyclic nucleotides in smooth muscle from protein kinase G deficient mice. J. Biol.Chem.  279:5146-5151 .[View Entrez Listing]

Gorenne I, Nakamoto RK, Phelps CP, Beckerle MC, Somlyo AV, Somlyo AP.(2003)  LPP, a LIM protein highly expressed in smooth muscle.  Am J Physiol Cell Physiol.  285:C674-85.  [View Entrez Listing]

Sheng, S., Gao, Y., Khromov, A.S., Somlyo, A.V., Somlyo, A.P., and Shao, Z. (2003)  Cryo atomic force microscopy of unphosphorylated and thiophosphorylated single smooth muscle myosin molecules.  J. Biol. Chem. 278:39892-39896. [View Entrez Listing]

Somlyo, A.P. and Somlyo, A.V. (2003) Ca2+-sensitivity of Smooth and Non-muscle Myosin II: Modulation by G Proteins, Kinases and Myosin Phosphatase.  Physiological Reviews   83:1325-1558. [View Entrez Listing]

Ho, R., Fan, D., Somlyo, A.V., and Somlyo, A.P. (2003) Calcium content of peripheral and central mitochondria in the guinea pig myocardium: electron probe analysis.  Cell Calcium 33:247-256. [View Entrez Listing]

Akar,  J.G.,  Everett, T.H., Ho, R., Craft, J., Haines, D.E., Somlyo, A.P., and Somlyo, A.V.  (2003) Intracellular chloride accumulation and subcellular elemental distribution during atrial fibrillation.   Circulation 107(13):1810-15  [View Entrez Listing]

Somlyo AV, Phelps C, diPierro C, Eto M, Read P, Barrett M, Gibson J, Burnitz MC, Myers C, Somlyo AP. (2003) Rho Kinase and Matrix Metalloproteinase Inhibitors Cooperate to Inhibit Angiogenesis and Growth of Human Prostate Cancer Xenotransplants. FASEB J 17:223-234.[ View Entrez Listing]

Somlyo, AV. (2002) New roads leading to Ca2+ sensitization. Circ. Res. 91:83-4. [View Entrez Listing]

 Wang H, Eto M, Steers WD, Somlyo AP, Somlyo AV. (2002) RhoA-mediated Ca2+  Sensitization in Erectile Function. J Biol Chem. 277(34):30614-30621 [View Entrez Listing]

Somlyo AP, Somlyo AVS.(2002)The sarcoplasmic reticulum: then and now. Novartis Found Symp. 2002;246:258-68; discussion 268-71, 272-6 .[View Entrez Listing]

Jo M, Thomas KS, Somlyo AV, Somlyo AP, Gonias SL. (2002) Cooperativity between the Ras-ERK and Rho-Rho kinase pathways in urokinase-type plasminogen activator-stimulated cell migration. J Biol Chem. 277:12479-12485 [View Entrez Listing]

Walker, L.A., MacDonald, J.A., Liu, X., Nakamoto, R.K., Haystead,T.A.J., Somlyo, A.V. and Somlyo, A.P. (2001) Site-specific phosphorylation and point mutations of telokin modulate itsCa2+-desensitizing effect in smooth muscle. J. Biol. Chem.276:24519-24524. [View Entrez Listing]

MacDonald, J.A., Borman, M.A., Muranyi, A., Somlyo, A.V., Hartshorne, D.J., and Haystead, T.A.J. (2001) Identification of the endogenous smooth muscle myosin phosphatase-associated kinase. Proc. Natl. Acad. Sci. 98:2419-2424. [View Entrez Listing]

Gong, M.C., Gorenne, I., Read, P., Jia, T., Nakamoto, R. K., Somlyo, A.V., and Somlyo, A.P. (2001) Regulation by GDI of RhoA/Rho-kinase-induced Ca2+-sensitization of smooth muscle myosin II. Am. J. Physiol. Cell Physiol. 281:C257. [View Entrez Listing]

Khromov, A.S., Somlyo, A.P. and Somlyo, A.V. (2001) Photolytic release of MgADP reduces rigor force in smooth muscle. Biophys. J. 80:1905-1914. [View Entrez Listing]

Shi D, Somlyo AV, Somlyo AP, Shao Z. (2001) Visualizing filamentous actin on lipid bilayers by atomic force microscopy in solution. J Microsc. 201(3):377-82. [View Entrez Listing]

Mack, C.P., Somlyo, A.V., Hautmann, M., Somlyo, A.P., and Owens, G.K. (2000) Smooth muscle differentiation marker gene expression is regulated by RhoA-mediated actin polymerization. J. Biol. Chem. 276:341-347. [View Entrez Listing]

MacDonald, J.A., Walker, L.A., Nakamoto, R.K., Gorenne, I., Somlyo, A.V., Somlyo, A.P., and Haystead, T.A.J. (2000) Phosphorylation of telokin by cyclic nucleotide kinases and the identification of in vivo phosphorylation sites in smooth muscle. FEBS Ltr. 479:83-88. [View Entrez Listing]

Matthew,J.D., Khromov, A.S., McDuffie, M.J., Somlyo, A.V., Somlyo, A.P., Taniguchi, S., and Takahashi, K. (2000) Contractile properties and proteins of smooth muscles of a calponin knockout mouse J. Physiol. 529:811-824. [View Entrez Listing]

Shao, Z., Shi, D. and Somlyo, A.V. (2000) Cryoatomic force microscopy of filamentous actin. Biophys. J. 78:950-959. [View Entrez Listing]

Nguyen, D.H.D., Catling, A.D., Webb, D.J., Sankovic, M., Walker, L.A., Somlyo, A.V., Weber, M.J. and Gonias, S.L. (1999) Myosin light chain kinase functions downstream of Ras/ERK to promote migration of urokinase-type plasminogen activator-stimulated cells in an integrin-selective manner. J. Cell Biol. 146:149-164. [View Entrez Listing]

Somlyo, A.P. and Somlyo, A.V. (2000) Signal transduction by G-proteins, Rho-kinase and protein phosphatase to smooth muscle and non-muscle myosin II. J. Physiol.522:177-185. [View Entrez Listing]

Read, P.W., Liu, X., Longenecker, K., DiPierro, C. G., Walker, L.A., Somlyo, A.V., Somlyo, A.P., and Nakamoto, R.K. (2000) Human RhoA/RhoGDI complex expressed in yeast: GTP exchange is sufficient for translocation of RhoA to liposomes. Protein Sci.9:1-11. [View Entrez Listing]

Somlyo, A.V., Bradshaw, D., Ramos, S., Murphy, C., Myers, C.E., and Somlyo, A.P. (2000) Rho-kinase inhibitor retards migration and in vivo dissemination of human prostatic cancer cells. Biochem. Biophys. Res. Commun. 269:652-659. [View Entrez Listing]

Longenecker, K., Read, P, Derewenda, U. , Dauter, Z., Liu, X., Garrard, S., Walker, L., Somlyo, A.V., Nakamoto, R. K., Somlyo, A.P., Derewenda, Z.S. (1999) How RhoGDI binds Rho. Acta Cryst. D55:1503-1515. [View Entrez Listing]

Fu, X., Gong, M.C., Jia, T., Somlyo, A.v. and Somlyo, A.P. (1998) The effects of the Rho-kinase inhibitor Y-27632 on arachidonic acid-, GTPgS-, and phorbol ester-induced Ca2+-sensitization of smooth muscle. FEBS Lett. 440:183-187. [View Entrez Listing]

Matthew, J.D., Khromov, A.S., Trybus, K.M., Somlyo, A.P. and Somlyo, A.V. (1998) Myosin essential light chain isoforms modulate the velocity of shortening propelled by nonphosphorylated crossbridges. J. Biol. Chem. 273:31289-31296. [View Entrez Listing]

He., Z.-H., Ferenczi, M.A., Brune, M., Trentham, D.R., Webb, M.R., Somlyo, A.P. and Somlyo, A.V. (1998) Time-resolved measurements of phosphate release by cycling cross-bridges in portal vein smooth muscle. Biophys. J. 75:3031-3040. [View Entrez Listing]

Somlyo, A.P. and Somlyo, A.V. (1998) From pharmacomechanical coupling to G-proteins and myosin phosphatase. Acta Physiol. Scand. 164:437-448. [View Entrez Listing]

Somlyo, A.V., Matthew, J.D., Wu, X., Khromov, A.S. and Somlyo, A.P. (1998) Regulation of the crossbridge cycle: the effects of MgADP, LC17 isoforms and telokin. Acta Physiol. Scand. 164:381-388. [View Entrez Listing]

Khromov, A., Somlyo, A.V. and Somlyo, A.P. (1998) MgADP promotes a catch-like state developed through force-calcium hysteresis in tonic smooth muscle. Biophys. J. 75:1926-1934. [View Entrez Listing]

Khromov, A.S., Somlyo, A.V. and Somlyo, A.P. (1998) Thiophosphorylation of myosin light chain increases rigor stiffness of rabbit smooth muscle. J. Physiol. 512:345-350. [View Entrez Listing]

Somlyo, A.P., Wu, X., Walker, L. and Somlyo, A.V. (1998) Pharmacomechanical coupling: the role of calcium, G-proteins, kinases and phosphatases. Rev. Physiol. Biochem. Pharmacol. 134:203-236. [View Entrez Listing]

Walker, L.A., Gailly, P., Jensen, P.E., Somlyo, A.V. and Somlyo, A.P. (1998) The unimportance of being (protein kinase C) epsilon. FASEB J. 12:813-821. [View Entrez Listing]

Wu, X., Haystead, T.A.J., Nakamoto, R.K., Somlyo, A.V. and Somlyo, A.P. (1998) Acceleration of myosin light chain dephosphorylation and relaxation of smooth muscle by telokin: synergism with cyclic nucleotide-activated kinase. J. Biol. Chem. 273:11362-11369. [View Entrez Listing]

Horikawa, Y., Goel, A., Somlyo, A.P. and Somlyo, A.V. (1998) Mitochondrial calcium in relaxed and tetanized myocardium. Biophys. J. 74:1579-1590. [View Entrez Listing]

Wei, Y., Zhang, Y., Derewenda, U., Liu, X., Minor, W., Nakamoto, R.K., Somlyo, A.V., Somlyo, A.P. and Derewenda, Z.S. (1997) Crystal structure of RhoA-GDP and its functional implications. Nature Struct. Biol. 4:699-703. [View Entrez Listing]

Lesh, R.E., Nixon, G.F., Fleischer, S., Airey, J.A., Somlyo, A.P. and Somlyo, A.V. (1997) Localization of ryanodine receptors in smooth muscle. Circ. Res. 82:175-185. [View Entrez Listing]

Fujihara, H., Walker, L.A., Gong, M.C., Lemichez, E., Boquet, P., Somlyo, A.V. and Somlyo, A.P. (1997) Inhibition of RhoA translocation and calcium sensitization by in vivo ADP-ribosylation with the chimeric toxin DC3B. Mol. Biol. Cell 8:2437-2447. [View Entrez Listing]

Gong, M.C., Fujihara, H., Somlyo, A.V. and Somlyo, A.P. (1997) Translocation of rhoA associated with Ca2+-sensitization of smooth muscle. J. Biol. Chem. 272:10704-10709. [View Entrez Listing]

Zhang, Y., Shao, Z., Somlyo, A.P. and Somlyo, A.V. (1997) Cryo-atomic force microscopy of smooth muscle myosin. Biophys. J. 72:1308-1318. [View Entrez Listing]

Gailly, P., Gong, M.C., Somlyo, A.V. and Somlyo, A.P. (1997) Possible role of atypical protein kinase C activated by arachidonic acid in Ca2+-sensitization of rabbit smooth muscle. J. Physiol. 500:95-110. [View Entrez Listing]

Gong, M.C., Fujihara, H., Walker, L.A., Somlyo, A.V. and Somlyo, A.P. (1997) Down regulation of G-protein-mediated Ca2+-sensitization in smooth muscle. Mol. Biol. Cell 8:279-286. [View Entrez Listing]

Somlyo, A.P. and Somlyo, A.V. (1996) Cellular and molecular mechanisms of smooth muscle. In: Alcohol and the Cardiovascular System. S. Zakhara and M. Wassef, Eds. NIH: Bethesda, MD, pp. 461-478.

Jensen, P.E., Gong, M.C., Somlyo, A.V. and Somlyo, A.P. (1996) Separate upstream and convergent downstream pathways of G-protein and phorbol ester-mediated Ca2+-sensitization of myosin light chain phosphorylation in smooth muscle. Biochem. J. 318:469-475. [View Entrez Listing]

Gailly, P., Wu, X., Haystead, T., Somlyo, A.P., Cohen, P. andSomlyo, A.V. (1996) Regions of the M110 subunit required for regulation of myosin light chain phosphatase activity in smooth muscle. Eur. J. Biochem. 239:326-332. [View Entrez Listing]

Khromov, A.S., Somlyo, A.V. and Somlyo, A.P. (1996) Nucleotide binding by actomyosin as a determinant of relaxation kinetics of phasic and tonic smooth muscle. J. Physiol. 492:669-673. [View Entrez Listing]

Wu, X., Somlyo, A.V. and Somlyo, A.P. Somlyo (1996) Cyclic GMP-dependent stimulation reverses G-protein-coupled inhibition of smooth muscle myosin light chain phosphatase. Biochem. Biophys. Res. Comm. 220: 658-663. [View Entrez Listing]

Gong, M.C., Iizuka, K., Nixon, G., Browne, J.P., Hall, A., Eccleston, J.F., Sugai, M., Kobayashi, S., Somlyo, A.V. and Somlyo, A.P. (1996) Role of guanine nucleotide-binding proteins–ras-family or trimeric or both–in Ca2+-sensitization of smooth muscle. Proc. Natl. Acad. Sci. USA 93:1340-1345. [View Entrez Listing]

Khromov, A., Somlyo, A.V., Trentham, D.R., Zimmermann, B. and Somlyo, A.P. (1995) The role of MgADP in force maintenance by dephosphorylated crossbridges in smooth muscle: a flash photolysis study. Biophys. J.69:2611-2622. [View Entrez Listing]

Zimmermann, B., Somlyo, A.V., Ellis-Davies, G.C.R., Kaplan, J.H. and Somlyo, A.P. (1995) Kinetics of prephosphorylation reactions and myosin light chain phosphorylation in smooth muscle: Flash photolysis studies with caged calcium and caged ATP. J. Biol. Chem. 270:23966-23974. [View Entrez Listing]

Somlyo, A.V. and Walz, B. (1995) Preface: Ca2+ in visual transduction and adaptation in vertebrates and invertebrates. Cell Calc. 18:253-255. [View Entrez Listing]

Lesh, R.E., Somlyo, A.P., Owens, G.K. and Somlyo, A.V. (1995) Reversible permeabilization: A novel technique for the intracellular introduction of antisense oligodeoxynucleotides into intact smooth muscle. Circ. Res. 77:220-230. [View Entrez Listing]

Gong, M.C., Kinter, M.T., Somlyo, A.V. and Somlyo, A.P. (1995) Arachidonic acid and diacylglycerol release associated with inhibition of myosin light chain dephosphorylation in rabbit smooth muscle J. Physiol. (Lond.) 486:113-122. [View Entrez Listing]

Somlyo, A.P., Gong, M.C., Iizuka, K., Haystead, T. and Somlyo, A.V.(1995) Pharmacomechanical coupling through regulation of myosin light chain phosphatase. Eds. In: Regulation of the Contractile Cycle in Smooth Muscle Springer-Verlag Tokyo pp.175-185. (Mie Symposium, April 1994)

Somlyo, A.V., Nishiye, E., Khromov, A., Somlyo, A.P. (1995) Cross-bridge cycle in phasic and tonic smooth muscle. T. Nakano and D.J. Hartshorne, Eds. In: Regulation of the Contractile Cycle in Smooth Muscle Springer-Verlag Tokyo pp. 73-84. (Mie Symposium, April 1994)

Shirazi, A., Iizuka, K., Mosse, C., Fadden, P., Somlyo, A.P., Somlyo, A.V. and Haystead, T. A.J. (1994) Purification and characterization of the mammalian myosin light chain phosphatase holoenzyme: The differential effects of the holoenzyme and its subunits on smooth muscle. J. Biol. Chem. 269:31598-31606. [View Entrez Listing]

Iizuka, K., Ikebe, M., Somlyo, A.V. and Somlyo, A.P. (1994) Introduction of high molecular weight (IgG) proteins into receptor coupled, permeabilized smooth muscle. Cell Calcium 16:431-445. [View Entrez Listing]

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Somlyo, A.P. and Somlyo, A.V. (1994) Signal transduction and regulation in smooth muscle. Nature 372:231-236. [View Entrez Listing]

Somlyo, A.P. and Somlyo, A.V. (1994) Signal transduction and the crossbridge cycle in smooth muscle. K. Maruyama, Y. Nonomura and K. Kohama, Eds. In: Calcium as Cell Signal, Proc. Yamada Conf. on Calcium as Cell Signal, Tokyo, Japan. Published by Igaku-Shoin, Tokyo, pp. 194-206.

Nixon, G., Mignery, G.A. and Somlyo, A.V. (1994) Immunogold localization of inositol 1,4.5-trisphosphate receptors and characterization of ultrastructural features of the sarcoplasmic reticulum in phasic and tonic smooth muscle. Running title: InsP3 receptor localization and SR structure in smooth muscle. J. Mus. Res. Cell Motil..15:682-700. [View Entrez Listing]

Somlyo, A.V. and Somlyo, A.P. (1993) Intracellular Signaling in Vascular Smooth Muscle. In: Interactive Phenomena in the Cardiac System. Ed. S. Sideman and R. Beyar, Plenum Publ. Corp. Chapter 4 p.p.31-38. (Advances in Experimental Medicine 346:31-36, 1993) [View Entrez Listing]

Somlyo, A. V. (1993) Modulation of the Ca2+ Switch: By G Proteins, Kinase and Phosphatase. NIPS 8:2.

Zhao, L., Wang, Y. Y., Ho, R., Shao, Z., Somlyo, A. V. and Somlyo, A. P. (1993) Thickness determination of biological thin sections by multiple least-squares fit of the carbon K-edge in the electron energy loss spectrum. Ultramicroscopy 48:290-296. [View Entrez Listing]

Lesh, R., Marks, A., Somlyo, A. V., Fleischer, S. and Somlyo, A. P. (1993) Anti-ryanodine antibody binding sites in vascular and endocardial endothelium. Circ. Res. 72: 481-488. [View Entrez Listing]

Nishiye, E., Somlyo, A. V., Török, K. and Somlyo, A. P. (1993) The effects of MgADP on cross-bridge kinetics: A laser flash photolysis study of guinea-pig smooth muscle. J. Physiol. 460: 247-271. [View Entrez Listing]

Collins, A., Somlyo, A. V. and Hilgemann, D. W. (1992) The giant cardiac membrane patch methods: Stimulation of outward Na+- Ca2+ exchange current by MgATP. J. Physiol. 454: 27-57. [View Entrez Listing]

Yang, J., Somlyo, A.V., Reedy, M. K., Takeyasu, K., Tamm, L.K., Alietta, M., Tillack, T.W., Shao, Z., (1992) Biological Application of Atomic-Force Microscopy.

Somlyo, A. V., Horiuti, K., Trentham, D. R., Kitazawa, T. and Somlyo, A. P. (1992) Kinetics of Ca2+-release and contraction induced by photolysis of caged D-myo-inositol 1, 4, 5-trisphosphate in smooth muscle: The effects of heparin, procaine, and adenine nucleotides. J. Biol. Chem. 267: 22316-22322. [View Entrez Listing]

Somlyo, A. V., Nishiye, E. and Somlyo, A. P. (1992) Myosin in smooth muscle: From thick filaments to the cross-bridge cycle. Jpn. J. Pharmacol. 58/S2: P41-P46. [View Entrez Listing]

Somlyo, A. P., Somlyo, A. V. (1992) Pharmacomechanical coupling: The role of G-proteins in Ca2+-release and modulation of Ca2+-sensitivity. Jpn. J. Pharmacol. 58/S2: P54-P59. [View Entrez Listing]

Ziegler, A., Somlyo, A. V. and Somlyo, A. P. (1992) Beta-adrenergic effects on cellular Na, Mg, Ca, K and Cl in vascular smooth muscle: Electron probe analysis of rabbit pulmonary artery. Cell Calcium 13: 593-602. [View Entrez Listing]

Gong, M. C., Fuglsang, A., Alessi, D., Kobayashi, S., Cohen, P., Somlyo, A. V. and Somlyo, A. P. (1992) Arachidonic acid inhibits myosin light chain phosphatase and sensitizes smooth muscle to calcium. J. Biol. Chem. 267(30): 21492-21498. [View Entrez Listing]

Gong, M. C., Cohen, P., Kitazawa, T., Ikebe, M., Masuo, M., Somlyo, A. P. and Somlyo, A. V. (1992) Myosin light chain phosphatase activities and the effects of phosphatase inhibitors in tonic and phasic smooth muscle. J. Biol. Chem. 267(21): 14662-14668. [View Entrez Listing]

Somlyo, A. P. and Somlyo, A. V. (1991) Compositional mapping in biology with a field emission TEM. Electron Optics Bulletin: Field Emission TEM 130: 40-44.

Somlyo, A. P., Kitazawa, T., Kobayashi, S. and Somlyo, A. V. (1991) Pharmacomechanical Coupling: The membranes talk to the crossbridges. Regulation of Smooth Muscle Contraction. Moreland Symposium, Plenum Press, Philadelphia, Pa. pp.185-208.

Somlyo, A. P. and Somlyo, A. V. (1991) Smooth muscle structure and function. The Heart and Cardiovascular System. Second Edition. H. A. Fozzard, ed. Raven Press, New York, NY. Chapter 48, pp. 1295-1324.

Baumann, O., Walz, B., Somlyo, A. V. and Somlyo, A. P. (1991) Electron probe microanalysis of calcium release and magnesium uptake by endoplasmic reticulum in bee photoreceptors. Proc. Natl. Acad. Sci. USA. 88:741-744. [View Entrez Listing]

Kobayashi, S., Gong, M. C., Somlyo, A. V. and Somlyo, A. P. (1991) Ca2+-channel blockers distinguish between G-protein-coupled, pharmacomechanical Ca2+ release and Ca2+ sensitization in smooth muscle. Am. J. Physiol. 260: C364-C370. [View Entrez Listing]

Somlyo, A. P and Somlyo, A. V. (1990) Flash photolysis studies on excitation-contraction coupling, regulation and contraction in smooth muscle. Annu. Rev. Physiol. 52: 857-874. [View Entrez Listing]

Somlyo, A. V., Horiuti, K., Kitazawa, T., Trentham, D. R. and Somlyo, A. P. (1990) Kinetics of InsP3-induced Ca2+ release in smooth muscle isolated from guinea-pig portal vein. J. Physiol. 429: 14.

Somlyo, A. P. and Somlyo, A. V. (1990) Excitation and contraction in smooth muscle. The Pulmonary Circulation: Normal and Abnormal. A. P. Fishman, ed. Univ. of Pennsylvania Press, pp. 31-40.

Kobayashi, S., Kitazawa, T., Somlyo, A. V., and Somlyo, A. P. (1989) Cytosolic heparin inhibits muscarinic and a-adrenergic Ca2+ release in smooth muscle: Physiological role of inositol 1,4,5-trisphosphate in pharmacomechanical coupling. J. Biol. Chem. 264: 17997-18004. [View Entrez Listing]

Horiuti, K., Somlyo, A. V., Goldman, Y. E., and Somlyo, A. P. (1990) Kinetics of contraction initiated by flash photolysis of caged adenosine trisphosphate in tonic and phasic smooth muscle. J. Gen. Physiol. 94: 769-781. [View Entrez Listing]

Somlyo, A. V., Kitazawa, T., Horiuti, K., Kobayashi, S., Trentham, D. R. and Somlyo, A. P. (1989) Heparin-sensitive inositol trisphosphate signaling and the role of G-proteins in Ca2+-release and contractile regulation in smooth muscle. Prog. Clin. Biol. Res. 327:167-182. [View Entrez Listing]

Takai, A., Troschka, M., Mieskes, G. and Somlyo, A. V. (1989) Protein phosphatase composition in the smooth muscle of guinea-pig ileum studied with okadaic acid and inhibitor 2. Biochem. J. 262: 617-623. [View Entrez Listing]

Jorgensen, A. P., Broderick, R., Somlyo, A. P. and Somlyo, A. V. (1988) Two structurally distinct calcium storage sites in rat cardiac sarcoplasmic reticulum. An electron microscope analysis study. Circ. Res. 63: 1060-1069. [View Entrez Listing]

Somlyo, A. V., Broderick, R., Shuman, H., Buhle, E.L., Jr. and Somlyo, A. P. (1988) Atrial specific granules in-situ have high calcium content, are acidic and maintain anion gradients. Proc. Natl. Acad. Sci. USA 85: 6222-6226. [View Entrez Listing]

Somlyo, A. V., Goldman, Y. E., Fujimori, T., Bond, M., Trentham, D. R. and Somlyo, A. P. (1988) Crossbridge kinetics, cooperactivity and negatively strained crossbridges in vertebrate smooth muscle: A laser flash photolysis study. J. Gen. Physiol. 91: 165-192. [View Entrez Listing]

Somlyo, A. V. and Somlyo, A. P. (1986) Electron optical studies on calcium and other ion movements in the sarcoplasmic reticulum in-situ. Sarcoplasmic Reticulum in Muscle Physiology. M. L. Entman and W. B. van Winkle, eds., CRC Press, Inc., Boca Raton, Fla., pp. 31-50.

Somlyo, A. V., McClellan, G., Gonzalez-Serratos, H. and Somlyo, A. P. (1985) Electron probe x-ray microanalysis of post-tetantic Ca and Mg movements across the sarcoplasmic reticulum in-situ.. J. Biol Chem. 260: 6801-6807. [View Entrez Listing]

Somlyo, A. V., Bond, M., Somlyo, A. P. and Scarpa, A. (1985) Inositol-trisphosphate (InsP3) induced calcium release and contraction in vascular smooth muscle. Proc. Natl. Acad. Sci. 82: 5231-5235. [View Entrez Listing]

Somlyo, A. V. and Franzini-Armstrong, C. (1985) New views of smooth muscle structure using freezing, deep-etching and rotary shadowing. Experientia 41: 841-856. [View Entrez Listing]

Somlyo, A. P., Bond, M. and Somlyo, A. V. (1985) The calcium content of mitochondria and endoplasmic reticulum in liver rapidly frozen in-situ. Nature 314: 622-625. [View Entrez Listing]

Kitazawa, T., Somlyo, A. P. and Somlyo, A. V. (1984) The effects of valinomycin on ion movements across the sarcoplasmic reticulum in frog muscle. J. Physiol. (London) 350: 253-268. [View Entrez Listing]

Bond, M., Shuman, H., Somlyo, A. P. and Somlyo, A. V. (1984) Total cytoplasmic calcium in relaxes and maximally contracted rabbit portal vein smooth muscle. J. Physiol. (London) 357: 185-201. [View Entrez Listing]

Bond, M., Kitazawa, T., Somlyo, A. P., and Somlyo, A. V. (1984) Release and recycling of calcium by the sarcoplasmic reticulum in guinea-pig portal vein smooth muscle. J. Physiol. (London) 355: 677-695. [View Entrez Listing]

Bond, M. and Somlyo, A. V. (1982) Dense bodies and actin polarity in vertebrate smooth muscle. J. Cell Biol. 95: 403-413. [View Entrez Listing]

Somlyo, A. V., Gonzalez-Serratos, H., Shuman, H., McClellan, G. and Somlyo, A. P. (1981) Calcium release and ionic changes in the sarcoplasmic reticulum of tetanized muscle: An electron probe study. J. Cell Biol. 90: 577-594. [View Entrez Listing]

Somlyo, A. V., Butler, T. M., Bond, M. and Somlyo, A. P. (1981) Myosin filaments have non-phosphorylated light chains in relaxed smooth muscle. Nature 294: 567-570. [View Entrez Listing]

Somlyo, A. V. (1980) Ultrastructure of vascular smooth muscle. The Handbook of Physiology: The Cardiovascular System, Vol. II: Vascular Smooth Muscle. D.F. Bohr, A.P. Somlyo, and H.V. Sparks, eds., American Physiological Society, Bethesda, Md., pp. 33-67.

Somlyo, A. V. (1979) Bridging structures spanning the junctional gap at the triad of skeletal muscle. J. Cell Biol. 80: 743-750. [View Entrez Listing]

Somlyo, A. V., Gonzalez-Serratos, H., McClellan, G., Shuman, H., Borrerro, L. M. and Somlyo, A. P. (1978) Electron probe analysis of the sarcoplasmic reticulum and vacuolated T-tubule system of fatigued frog muscles. Ann. N.Y. Acad. Sci. 307: 232-235.

Somlyo, A. V., Shuman, H. and Somlyo, A. P. (1977) Composition of the sarcoplasmic reticulum in situ: Electron probe x-ray microanalysis of cryosections. Nature 268: 556-558. [View Entrez Listing]

Somlyo, A. V., Shuman, H. and Somlyo, A. P. (1977) Elemental distribution in striated muscle and effects of hypertonicity: Electron probe analysis of cryosections. J. Cell Biol. 74: 828-857. [View Entrez Listing]

Somlyo, A. V., Ashton, F. T., Lemanski, L., Vallieres, J. and Somlyo, A. P. (1977) Filament organization and dense bodies in vertebrate smooth muscle. Biochemistry of Smooth Muscle, pp 445-471. N.L. Stephens, ed., Univ. Park Press, Baltimore, MD.

Somlyo, A. V. (1977) The contractile apparatus of vascular smooth muscle. Mechanisms of Vasodilation., pp. 12-20. P. Vanhoutte and I. Leusen, eds., Basel, Switzerland: S. Karger AG.

Ashton, F. T., Somlyo, A. V. and Somlyo, A. P. (1974) The contractile apparatus of vascular smooth muscle: Intermediate high voltage stereo electron microscopy. J. Mol. Biol. 98: 17-29. [View Entrez Listing]

Somlyo, A. V. and Somlyo, A. P. (1971) Strontium accumulation by sarcoplasmic reticulum and mitochondria in vascular smooth muscle. Science 174: 955-958. [View Entrez Listing]

Friedmann, N., Somlyo, A.V. and Somlyo, A.P. (1971) Cyclic adenosine and guanosine monophosphates and gucagon: effect on liver membrane potentials. Science 171:400-402. [View Entrez Listing]

Somlyo, A. P. and Somlyo, A. V. (1970) Vascular smooth muscle: II. Pharmacology of normal and hypertensive vessels. Pharmacol. Rev. 22: 249-353. [View Entrez Listing]

Somlyo, A. V. and Somlyo, A. P. (1968) Electromechanical and pharmacomechanical coupling in vascular smooth muscle. J. Pharmacol. Exp. Therap. 159: 129-145. [View Entrez Listing]

Somlyo, A. P. and Somlyo, A. V. (1968) Vascular smooth muscle: I. Normal structure, pathology, biochemistry and biophysics. Pharmacol. Rev. 20: 197-272. [View Entrez Listing]