Divergent regulation of the sarcomere and the cytoskeleton.
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.
Schevzov
Galina
G
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.
Fath
Thomas
T
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.
Vrhovski
Bernadette
B
Oncology Research Unit, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales 2145, Australia.
Vlahovich
Nicole
N
Muscle Development Unit, The Children's Medical Research Institute, Locked Bag 23, Wentworthville, New South Wales 2145, Australia, the.
Rajan
Sudarsan
S
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, Ohio 45267-0524.
Hook
Jeff
J
Oncology Research Unit, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales 2145, Australia.
Joya
Josephine E
JE
Muscle Development Unit, The Children's Medical Research Institute, Locked Bag 23, Wentworthville, New South Wales 2145, Australia, the.
Lemckert
Frances
F
Oncology Research Unit, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales 2145, Australia.
Puttur
Franz
F
Oncology Research Unit, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales 2145, Australia.
Lin
Jim J-C
JJ
Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52242-1324.
Hardeman
Edna C
EC
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.
Wieczorek
David F
DF
Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, Ohio 45267-0524.
O'Neill
Geraldine M
GM
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.
Gunning
Peter W
PW
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.
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
D000199:Actins; D020033:Protein Isoforms; C411923:Tpm3 protein, mouse; D014335:Tropomyosin; C515376:tropomyosin 4 protein, mouse