Publication Date:
2012-08-28
Description:
The heart's pumping capacity results from highly regulated interactions of actomyosin molecular motors. Mutations in the gene for a potential regulator of these motors, cardiac myosin-binding protein C (cMyBP-C), cause hypertrophic cardiomyopathy. However, cMyBP-C's ability to modulate cardiac contractility is not well understood. Using single-particle fluorescence imaging techniques, transgenic protein expression, proteomics, and modeling, we found that cMyBP-C slowed actomyosin motion generation in native cardiac thick filaments. This mechanical effect was localized to where cMyBP-C resides within the thick filament (i.e., the C-zones) and was modulated by phosphorylation and site-specific proteolytic degradation. These results provide molecular insight into why cMyBP-C should be considered a member of a tripartite complex with actin and myosin that allows fine tuning of cardiac muscle contraction.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561468/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3561468/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Previs, M J -- Beck Previs, S -- Gulick, J -- Robbins, J -- Warshaw, D M -- 8P20GM103449/GM/NIGMS NIH HHS/ -- HL007647/HL/NHLBI NIH HHS/ -- HL059408/HL/NHLBI NIH HHS/ -- P01 HL059408/HL/NHLBI NIH HHS/ -- P20 GM103449/GM/NIGMS NIH HHS/ -- R01 HL086728/HL/NHLBI NIH HHS/ -- T32 HL007647/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2012 Sep 7;337(6099):1215-8. doi: 10.1126/science.1223602. Epub 2012 Aug 23.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Molecular Physiology and Biophysics, University of Vermont, Burlington, VT 05405, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/22923435" target="_blank"〉PubMed〈/a〉
Keywords:
Actin Cytoskeleton/*physiology
;
Actomyosin/metabolism
;
Amino Acid Motifs
;
Animals
;
Carrier Proteins/chemistry/*metabolism
;
Mice
;
Mice, Transgenic
;
*Myocardial Contraction
;
Myocardium/*metabolism/ultrastructure
;
Myofibrils/*metabolism
;
Myosins/*metabolism
;
Phosphorylation
;
Proteolysis
;
Sarcomeres/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
