Divergent regulation of the sarcomere and the cytoskeleton

Galina Schevzov, Thomas Fath, Bernadette Vrhovski, Nicole Vlahovich, Sudarsan Rajan, Jeff Hook, Josephine E. Joya, Frances Lemckert, Franz Puttur, Jim J.-C. Lin, Edna C. Hardeman, David F. Wieczorek, Geraldine M. O'Neill, Peter W. Gunning*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

36 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)275-283
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number1
DOIs
Publication statusPublished - 4 Jan 2008
Externally publishedYes

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