title: Krp1 (Sarcosin) promotes lateral fusion of myofibril assembly intermediates in cultured mouse cardiomyocytes.
abstract: Krp1, also called sarcosin, is a cardiac and skeletal muscle kelch repeat protein hypothesized to promote the assembly of myofibrils, the contractile organelles of striated muscles, through interaction with N-RAP and actin. To elucidate its role, endogenous Krp1 was studied in primary embryonic mouse cardiomyocytes. While immunofluorescence showed punctate Krp1 distribution throughout the cell, detergent extraction revealed a significant pool of Krp1 associated with cytoskeletal elements. Reduction of Krp1 expression with siRNA resulted in specific inhibition of myofibril accumulation with no effect on cell spreading. Immunostaining analysis and electron microscopy revealed that cardiomyocytes lacking Krp1 contained sarcomeric proteins with longitudinal periodicities similar to mature myofibrils, but fibrils remained thin and separated. These thin myofibrils were degraded by a scission mechanism distinct from the myofibril disassembly pathway observed during cell division in the developing heart. The data are consistent with a model in which Krp1 promotes lateral fusion of adjacent thin fibrils into mature, wide myofibrils and contribute insight into mechanisms of myofibrillogenesis and disassembly.
authors.affiliation: National Institute of Arthritis and Musculoskeletal and Skin Diseases, Department of Health and Human Services, NIH, Bethesda, MD 20892, USA.
authors.forename: Cynthia C
authors.initials: CC
authors.lastname: Greenberg
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Connelly
authors.forename: Mathew P
authors.initials: MP
authors.lastname: Daniels
authors.forename: Robert
authors.initials: R
authors.lastname: Horowits
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D006321:Heart / Q000196:embryology; D051379:Mice; D008854:Microscopy, Electron; D009124:Muscle Proteins / Q000502:physiology*; D032383:Myocytes, Cardiac / Q000166:cytology*; D009210:Myofibrils / Q000378:metabolism* / Q000648:ultrastructure; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: D003598:Cytoskeletal Proteins; D009124:Muscle Proteins; D034741:RNA, Small Interfering; C528692:sarcosin protein, mouse