Abstract

The contraction of vertebrate smooth muscle, like all other types of muscle is the result of a cyclic interaction of the proteins myosin and actin in a process coupled to the hydrolysis of ATP. The regulation of smooth muscle contraction is very complex involving several distinct regulatory systems. Because of the great importance of the regulation of smooth muscle contraction, particularly in relation to vascular disease, the various components of these regulatory systems must be identified and the interactions which produce overall regulation must be defined. The primary regulatory system in smooth muscle appears to be myosin based with dephosphorylation of myosin causing relaxation. More evidence has been accumulating that an actin-linked system may further modulate the force producing interaction of myosin with actin. A likely candidate for an actin binding regulatory protein is the recently identified protein, caldesmon. The inhibitory function of caldesmon will be studied in detail. Its binding to actin and other proteins in the contractile apparatus will be quantitated. Finally, the interplay of myosin based and actin based regulatory systems in smooth muscle will be examined. Other potential regulatory proteins from smooth muscle may also be studied.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
5R01AR035216-02
Application #
3157108
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1985-04-01
Project End
1988-03-31
Budget Start
1986-04-01
Budget End
1987-03-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost

  Institution

Name
East Carolina University
Department
Type
Schools of Medicine
DUNS #
City
Greenville
State
NC
Country
United States
Zip Code
27858

  Publications

Kingsbury, Nathanial L; Renegar, Randall H; Chalovich, Joseph M (2013) Avian synaptopodin 2 (fesselin) stabilizes myosin filaments and actomyosin in the presence of ATP. Biochemistry 52:7641-7
Schroeter, Mechthild M; Orlova, Albina; Egelman, Edward H et al. (2013) Organization of F-actin by Fesselin (avian smooth muscle synaptopodin 2). Biochemistry 52:4955-61
Franklin, Andrew J; Baxley, Tamatha; Kobayashi, Tomoyoshi et al. (2012) The C-terminus of troponin T is essential for maintaining the inactive state of regulated actin. Biophys J 102:2536-44
Jung, Hyun Suk; Billington, Neil; Thirumurugan, Kavitha et al. (2011) Role of the tail in the regulated state of myosin 2. J Mol Biol 408:863-78
Chalovich, Joseph M; Lutz, Evan; Baxley, Tamatha et al. (2011) Acrylodan-labeled smooth muscle tropomyosin reports differences in the effects of troponin and caldesmon in the transition from the active state to the inactive state. Biochemistry 50:6093-101
Chalovich, Joseph M; Schroeter, Mechthild M (2010) Synaptopodin family of natively unfolded, actin binding proteins: physical properties and potential biological functions. Biophys Rev 2:181-189
Varughese, Jayson F; Chalovich, Joseph M; Li, Yumin (2010) Molecular dynamics studies on troponin (TnI-TnT-TnC) complexes: insight into the regulation of muscle contraction. J Biomol Struct Dyn 28:159-74
Hamden, Svetlana S; Schroeter, Mechthild M; Chalovich, Joseph M (2010) Phosphorylation of caldesmon at sites between residues 627 and 642 attenuates inhibitory activity and contributes to a reduction in Ca2+-calmodulin affinity. Biophys J 99:1861-8
Renegar, Randall H; Chalovich, Joseph M; Leinweber, Barbara D et al. (2009) Localization of the actin-binding protein fesselin in chicken smooth muscle. Histochem Cell Biol 131:191-6
Jung, Hyun Suk; Burgess, Stan A; Billington, Neil et al. (2008) Conservation of the regulated structure of folded myosin 2 in species separated by at least 600 million years of independent evolution. Proc Natl Acad Sci U S A 105:6022-6

Showing the most recent 10 out of 53 publications