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Originally published In Press as doi:10.1074/jbc.M704392200 on October 18, 2007

J. Biol. Chem., Vol. 283, Issue 1, 275-283, January 4, 2008
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Divergent Regulation of the Sarcomere and the Cytoskeleton*Formula

Galina Schevzov{ddagger}§, Thomas Fath{ddagger}§, Bernadette Vrhovski{ddagger}, Nicole Vlahovich, Sudarsan Rajan||, Jeff Hook{ddagger}, Josephine E. Joya, Frances Lemckert{ddagger}, Franz Puttur{ddagger}, Jim J.-C. Lin**, Edna C. Hardeman{ddagger}{ddagger}, David F. Wieczorek||, Geraldine M. O'Neill{ddagger}§, and Peter W. Gunning, A Principal Research Fellow of the NHMRC (Grant 163626){ddagger}§1

From the {ddagger}Oncology Research Unit, The Children's Hospital at Westmead, Locked Bag 4001, Westmead, New South Wales 2145, Australia, the §Discipline of Paediatrics and Child Health and the {ddagger}{ddagger}Faculty of Medicine, University of Sydney, Sydney, New South Wales 2006, Australia, the Muscle Development Unit, The Children's Medical Research Institute, Locked Bag 23, Wentworthville, New South Wales 2145, Australia, the ||Department of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, Ohio 45267-0524, the **Department of Biological Sciences, University of Iowa, Iowa City, Iowa 52242-1324

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.


Received for publication, May 29, 2007 , and in revised form, October 4, 2007.

* This work was supported in part by Australian National Health and Medical Research Council (NHMRC) Grants 117409 (to P. W. G.) and 321705 (to E. H.), a Career Development Fellowship from the New South Wales Cancer Council (to G. M. O.), National Institutes of Health Grant HL71952 (to D. F. W.), and funding from the Oncology Children's Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Formula The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1-S3.

1 To whom correspondence should be addressed. E-mail: PeterG3{at}chw.edu.au.


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