Thomas Jefferson University - Marion J. Siegman
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Marion J. Siegman
Physiology
Thomas Jefferson University
Jefferson Medical College
Department of Molecular Physiology and Biophysics
Professor
Appointed: 1967
Thomas Jefferson University
Jefferson Medical College
Department of Molecular Physiology and Biophysics
Chair Appointed: 2002
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Mailing Address
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1020 Locust Street
Philadelphia, Pennsylvania 19107
United States
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Expertise and Research Interests
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In disease states, such as hypertension, the primary defect may be traced to the regulation of the mechanisms for maintenance of tone in smooth muscle. The basic mechanisms controlling tone are not well understood. A unique and important characteristic of all smooth muscles is the ability to vary the energy cost of force production and maintenance during the time course of isometric contractions. It has become obviousthat there are many similarities among the mechanical and energetic properties of mammalian smooth muscles during the 'latch' state and molluscan muscles during 'catch,' yet the molecular basis of these states and their regulation is not well understood. A unique feature of catch muscle is the operation of a mechanism that appears to control the detachment rate of the crossbridge. Such a mechanism has not yet been identified in mammalian muscle, but would be of great importance as a means of regulating tone and consequently physiological functions, such as blood pressure. The elucidation of such a mechanism in catch thus has the potential to provide important insights into normal and abnormal function of the cardiovascular, pulmonary, digestive, and reproductive systems. We have discovered that the mini-titin 'twitchin' is key to the regulation of force production and catch. Twitchin is associated with myosin and is an integral part of the thick contractile filament. The overall goal of our research is to define the state of the myosin crossbridge and its kinetics of turnover at rest and during phasic and catch contractions in the anterior byssus retractor muscle ABRM of Mytilus edulis, and to identify the molecular mechanisms by which the phosphhorylation state of twitchin regulates transition of the crossbridge into and out of the catch state.
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Keywords
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Actin; Myosin; cAMP; Energetics of Contraction; Muscle Contraction; Muscle Relaxation; Myosin; High energy phosphates; Mollusca; Regulation of Smooth Muscle; Catch; Anterior byssus retractor muscle (ABRM); Twitchin; Ultrastructure of Muscle; Shortening;
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Publications
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- Butler,T.M. and Siegman, M.J. Mechanism of Catch Force: Tethering of Thick and Thin Filaments by Twitchin. J Biochemistry and Biotechnology, May 2010.
- Franke, A.S., Mooers, S.U. Narayan, S.R., Siegman, M.J. and Butler, T.M. Myosin crossbridge kinetics and the mechanism of catch. Biophys J. 93: 554-565, 2007
- Siegman, M.J., Franke, A.S., Mooers, S.U., Narayan, S.R., and Butler, T.M. Twitchin: a catch-maintaining link in invertebrate smooth muscle. J. Muscle Research & Cell Motility 28: 429-490, 2007
- Butler, T.M., Mooers, S.U. and Siegman, M.J. Catch force links and the low to high force transition of myosin. Biophysical Journal 90: 3193-3202, 2006.
- Funabara, D., Kanoh, S., Siegman, M.J., Butler, T.M., Hartshorne, D.J. and Watabe, S. Twitchin as a regulator of catch contraction in molluscan smooth muscle. J. Muscle Research and Cell Motililty 26: 455-460, 2005.
- Siegman
MJ, Hartshorne DJ. Andrew P. Somlyo (1930-2004). J Muscle Res Cell Motil. 2004;25(3):193-202. No abstract available.
- Funabara D, Watabe S, Mooers SU, Narayan S, Dudas C, Hartshorne DJ, Siegman MJ, Butler TM. Twitchin from Molluscan Catch Muscle. Primary Structure and Relationship between Site-Specific Phosphorylation and Mechanical Function. J Biol Chem. 2003 Aug 1;278(31):29308-16. Epub 2003
- Butler , T.M., S.R. Narayan, S.U. Mooers, D.J. Hartshorne and M.J. Siegman. The myosin cross-bridge cycle and its control by twitchin phosphorylation in catch muscle. Biophysical Journal. 80: 415-426, 2001
- Funabara , D., S. Kinoshita, S. Watabe, T.M. Butler, M.J. Siegman and D.J. Hartshorne. Phosphorylation of molluscan twitchin by the cAMP-dependent protein kinase. Biochemistry. 40: 2087-2095, 2001
- Butler TM; Siegman MJ. Control of cross-bridge cycling by myosin light chain phosphorylation in mammalian smooth muscle. Acta Physiologica Scandinavica. 164(4): 389-400, Dec 1998
- Siegman M J;Funabara D;Kinoshita S;Watabe S;Hartshorne D J;Butler T M. Phosphorylation of a twitchin-related protein controls catch and calcium sensitivity of force production in invertebrate smooth muscle. Proceedings of the National Academy of Sciences (USA). 95(9): 5383-8, 28 Apr 1998
- Siegman , M.J., Daisuke Siegman, M.J., Funabara, Shigeharu Kinoshita, Shugo Watabe, David J. Hartshorne and. Phosphorylation of a twitchin-related protein controls catch and calcium-. Proceedings of the National Academy of Sciences. 95:: 5383-5388, 1998
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- Butler , T.M., S.U. Mooers, Chenqing Li, S. Narayan, and M.J. Siegman. Regulation of catch muscle by Twitchin phosphorylation: Effects on force, ATPase, and shortening. Biophysical Journal. 75: 1904-1914, 1998
- Siegman M J;Mooers S U;Li C;Narayan S;Trinkle-Mulcahy L;Watabe S;Hartshorne D J;Butler T M. Phosphorylation of a high molecular weight (approximately 600 kDa) protein regulates catch in invertebrate smooth muscle. Journal of Muscle Research and Cell Motility. 18(6): 655-70, Dec 1997
- Siegman M J;Butler T M;Mooers S U;Trinkle-Mulcahy L;Narayan S;Adam L;Chacko S;Haase H;Morano I. Hypertrophy of colonic smooth muscle: contractile proteins, shortening velocity, and regulation. American Journal of Physiology. 272(6 Pt 1): G1571-80, Jun 1997
- Siegman M J;Butler T M;Mooers S U;Trinkle-Mulcahy L;Narayan S;Stirewalt W S;Starcher B C. Hypertrophy of colonic smooth muscle: structural remodeling, chemical composition, and force output. American Journal of Physiology. 272(6 Pt 1): G1560-70, Jun 1997
- Trinkle-Mulcahy L;Ichikawa K;Hartshorne D J;Siegman M J;Butler T M. Thiophosphorylation of the 130-kDa subunit is associated with a decreased activity of myosin light chain phosphatase in alpha-toxin-permeabilized smooth muscle. Journal of Biological Chemistry. 270(31): 18191-4, 4 Aug 1995
- Butler T M;Narayan S R;Mooers S U;Siegman M J. Rapid turnover of myosin light chain phosphate during cross-bridge cycling in smooth muscle. American Journal of Physiology. 267(4 Pt 1): C1160-6, Oct 1994
- Siegman M J;Mooers S U;Warren T B;Warshaw D M;Ikebe M;Butler T M. Comparison of the effects of 2,3-butanedione monoxime on force production, myosin light chain phosphorylation and chemical energy usage in intact and permeabilized smooth and skeletal muscles. Journal of Muscle Research and Cell Motility. 15(4): 457-72, Aug 1994
- Vyas T B;Mooers S U;Narayan S R;Siegman M J;Butler T M. Cross-bridge cycling at rest and during activation. Turnover of myosin-bound ADP in permeabilized smooth muscle. Journal of Biological Chemistry. 269(10): 7316-22, 11 Mar 1994
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- Vyas T B;Mooers S U;Narayan S R;Witherell J C;Siegman M J;Butler T M. Cooperative activation of myosin by light chain phosphorylation in permeabilized smooth muscle. American Journal of Physiology. 263(1 Pt 1): C210-9, Jul 1992
- Siegman M J;Vyas T B;Mooers S U;Butler T M. Energetics and regulation of smooth muscle contraction. (Review)Japanese Journal of Pharmacology. 58 Suppl 2: 75P-80P, 1992
- Siegman M J;Butler T M;Vyas T;Mooers S U;Narayan S. Cooperative mechanisms in the regulation of smooth muscle contraction. Advances In Experimental Medicine and Biology. 304: 77-84, 1991
- Butler T M;Siegman M J;Mooers S U;Narayan S R. Myosin-product complex in the resting state and during relaxation of smooth muscle. American Journal of Physiology. 258(6 Pt 1): C1092-9, Jun 1990
- Siegman M J;Butler T M;Mooers S U. Energetics as an approach to the study of smooth muscle: the Bozler legacy. Progress In Clinical and Biological Research. 327: 17-27, 1990
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Individual Expertise profile of
Marion J. Siegman, Copyright © Marion J. Siegman.
Last Updated
by Marion Siegman : Friday, April 23, 2010 9:53:27 AM
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