title: Divergent regulation of the sarcomere and the cytoskeleton.
abstract: The existence of a feedback mechanism regulating the precise amounts of muscle structural proteins, such as actin and the actin-associated protein tropomyosin (Tm), in the sarcomeres of striated muscles is well established. However, the regulation of nonmuscle or cytoskeletal actin and Tms in nonmuscle cell structures has not been elucidated. Unlike the thin filaments of striated muscles, the actin cytoskeleton in nonmuscle cells is intrinsically dynamic. Given the differing requirements for the structural integrity of the actin thin filaments of the sarcomere compared with the requirement for dynamicity of the actin cytoskeleton in nonmuscle cells, we postulated that different regulatory mechanisms govern the expression of sarcomeric versus cytoskeletal Tms, as key regulators of the properties of the actin cytoskeleton. Comprehensive analyses of tissues from transgenic and knock-out mouse lines that overexpress the cytoskeletal Tms, Tm3 and Tm5NM1, and a comparison with sarcomeric Tms provide evidence for this. Moreover, we show that overexpression of a cytoskeletal Tm drives the amount of filamentous actin.
authors.affiliation: Oncology Research Unit, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales 2145, Australia; Discipline of Paediatrics and Child Health, Sydney, New South Wales 2006, Australia.
authors.forename: Galina
authors.initials: G
authors.lastname: Schevzov
authors.affiliation: Oncology Research Unit, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales 2145, Australia; Discipline of Paediatrics and Child Health, Sydney, New South Wales 2006, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fath
authors.affiliation: Oncology Research Unit, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales 2145, Australia.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Vrhovski
authors.affiliation: Muscle Development Unit, The Children's Medical Research Institute, Locked Bag 23, Wentworthville, New South Wales 2145, Australia, the.
authors.forename: Nicole
authors.initials: N
authors.lastname: Vlahovich
authors.affiliation: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, Ohio 45267-0524.
authors.forename: Sudarsan
authors.initials: S
authors.lastname: Rajan
authors.affiliation: Oncology Research Unit, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales 2145, Australia.
authors.forename: Jeff
authors.initials: J
authors.lastname: Hook
authors.affiliation: Muscle Development Unit, The Children's Medical Research Institute, Locked Bag 23, Wentworthville, New South Wales 2145, Australia, the.
authors.forename: Josephine E
authors.initials: JE
authors.lastname: Joya
authors.affiliation: Oncology Research Unit, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales 2145, Australia.
authors.forename: Frances
authors.initials: F
authors.lastname: Lemckert
authors.affiliation: Oncology Research Unit, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales 2145, Australia.
authors.forename: Franz
authors.initials: F
authors.lastname: Puttur
authors.affiliation: Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52242-1324.
authors.forename: Jim J-C
authors.initials: JJ
authors.lastname: Lin
authors.affiliation: Muscle Development Unit, The Children's Medical Research Institute, Locked Bag 23, Wentworthville, New South Wales 2145, Australia, the; Faculty of Medicine, University of Sydney, Sydney, New South Wales 2006, Australia, the.
authors.forename: Edna C
authors.initials: EC
authors.lastname: Hardeman
authors.affiliation: Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, Ohio 45267-0524.
authors.forename: David F
authors.initials: DF
authors.lastname: Wieczorek
authors.affiliation: Oncology Research Unit, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales 2145, Australia; Discipline of Paediatrics and Child Health, Sydney, New South Wales 2006, Australia.
authors.forename: Geraldine M
authors.initials: GM
authors.lastname: O'Neill
authors.affiliation: Oncology Research Unit, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales 2145, Australia; Discipline of Paediatrics and Child Health, Sydney, New South Wales 2006, Australia. Electronic address: PeterG3@chw.edu.au.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Gunning
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012518:Sarcomeres / Q000378:metabolism*; D014335:Tropomyosin / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D020033:Protein Isoforms; C411923:Tpm3 protein, mouse; D014335:Tropomyosin; C515376:tropomyosin 4 protein, mouse