title: COOH-terminal truncated human cardiac MyBP-C alters myosin filament organization.
abstract: Myosin-binding protein C (MyBP-C) is thought to play structural and/or regulatory role in striated muscles. The cardiac isoform of MyBP-C is one of the disease genes associated with familial hypertrophic cardiomyopathy and most of the mutations produce COOH truncated proteins. In order to determine the consequences of these mutations on myosin filament organization, we have characterized the effect of a 52-kDa NH2-terminal peptide of human cardiac MyBP-C on the alpha-myosin heavy chain (alpha-MyHC) filament organization. This peptide lacks the COOH-terminal MyHC-binding site and retains the two MyHC-binding domains located in the N-terminal part of MyBP-C. For this characterization, cDNA constructs (rat alpha-MyHC, full-length and truncated human cardiac MyBP-C) were transiently expressed singly or in pairwise combination in COS cells. In conformity with previous works performed on the skeletal isoform of MyBP-C, we observed that full-length cardiac MyBP-C organizes the MyHC into dense structures of uniform width. While the truncated protein is stable and can interact with MyHC in COS cells, it does not result in the same organization of sarcomeric MyHC that is seen with the full-length MyBP-C. These results suggest that the presence of truncated cardiac MyBP-C could, at least partly, disorganize the sarcomeric structure in patients with familial hypertrophic cardiomyopathy.
authors: Inserm Unit 523, institut de myologie, hôpital Salpêtrière, bâtiment Babinski, 47, boulevard de l'Hôpital, 75651 Paris, France. sebilion@infobiogen.fr
authors: P
authors: P
authors: Sébillon
authors: G
authors: G
authors: Bonne
authors: J
authors: J
authors: Flavigny
authors: S
authors: S
authors: Venin
authors: A
authors: A
authors: Rouche
authors: M
authors: M
authors: Fiszman
authors: K
authors: K
authors: Vikstrom
authors: L
authors: L
authors: Leinwand
authors: L
authors: L
authors: Carrier
authors: K
authors: K
authors: Schwartz
mesh_terms: D008841:Actin Cytoskeleton / Q000502:physiology* / Q000648:ultrastructure; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D002522:Chlorocebus aethiops; D006321:Heart / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D009218:Myosins / Q000737:chemistry / Q000502:physiology*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D012518:Sarcomeres / Q000502:physiology* / Q000648:ultrastructure; D017384:Sequence Deletion; D014162:Transfection; D000099163:Myosin Binding Protein C
chemical_list: D002352:Carrier Proteins; D009218:Myosins; D020033:Protein Isoforms; D011994:Recombinant Proteins; D000099163:Myosin Binding Protein C