title: Ascribing novel functions to the sarcomeric protein, myosin binding protein H (MyBPH) in cardiac sarcomere contraction.
abstract: Myosin binding protein H (MyBPH) is a protein of unknown function, which shares sequence and structural similarities with myosin binding protein C (cMyBPC), a protein frequently implicated in hypertrophic cardiomyopathy (HCM). Given the similarity between cMyBPC and MyBPH, we proposed that MyBPH, like cMyBPC, could be involved in HCM pathogenesis and we therefore sought to determine its function. We identified MyBPH-interacting proteins by using yeast two-hybrid (Y2H) analysis. The role of MyBPH and cMyBPC in cardiac cell contractility was analysed by measuring the planar cell surface area of differentiated H9c2 rat cardiomyocytes in response to β-adrenergic stress after siRNA knockdown of MyBPH and cMyBPC. Individual knockdown of either protein had no effect on cardiac contractility, while concurrent knockdowns reduced cardiac contractility. These proteins therefore functionally compensate for one another and are critical for cardiac contractility. We further show that both proteins co-localise with the autophagosomal membrane protein LC3, suggesting that both proteins are involved in autophagosomal membrane maturation processes. The results of this study ascribe novel functions to MyBPH, which may contribute to our understanding of its role in the sarcomere. This study provides evidence for a potential role of MyBPH in HCM, which warrants further investigation.
authors.affiliation: DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 19063, Francie van Zijl Drive, Tygerberg 7505, South Africa. Electronic address: jomien@sun.ac.za.
authors.forename: Jomien
authors.initials: J
authors.lastname: Mouton
authors.affiliation: Department of Physiological Sciences, Stellenbosch University, Private Bag X1, Merriman Street, Stellenbosch 7602, South Africa. Electronic address: bloos@sun.ac.za.
authors.forename: Ben
authors.initials: B
authors.lastname: Loos
authors.affiliation: DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 19063, Francie van Zijl Drive, Tygerberg 7505, South Africa. Electronic address: braintrain100@gmail.com.
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Moolman-Smook
authors.affiliation: DST/NRF Centre of Excellence for Biomedical Tuberculosis Research, MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 19063, Francie van Zijl Drive, Tygerberg 7505, South Africa. Electronic address: gkin@sun.ac.za.
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Kinnear
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001343:Autophagy / Q000502:physiology; D002312:Cardiomyopathy, Hypertrophic / Q000473:pathology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009200:Myocardial Contraction / Q000235:genetics* / Q000502:physiology; D032383:Myocytes, Cardiac / Q000502:physiology*; D018995:Myosin Heavy Chains / Q000378:metabolism; D011485:Protein Binding; D034622:RNA Interference; D034741:RNA, Small Interfering; D051381:Rats; D012518:Sarcomeres / Q000502:physiology*; D020798:Two-Hybrid System Techniques; D044763:Ubiquitin-Conjugating Enzymes / Q000378:metabolism; D000098843:Ubiquitin-Conjugating Enzyme UBC9; D000099163:Myosin Binding Protein C
chemical_list: D000199:Actins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D008869:Microtubule-Associated Proteins; D018995:Myosin Heavy Chains; D034741:RNA, Small Interfering; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9; D000099163:Myosin Binding Protein C; C526109:Anxa3 protein, rat; C000594638:MYH7 protein, rat; C484118:Mybph protein, rat
keywords: Cardiac contractility; Cardiac myosin binding protein C; Hypertrophic cardiomyopathy; Myosin binding protein H; Protein–protein interaction