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Dynamic uncapping

Capping protein is removed rapidly from the ends of actin filaments.

The surge of actin growth toward the cell periphery is stopped abruptly by capping protein (CP). In vitro, this protein sticks like glue, but in vivo it comes off the ends of those filaments rapidly, say Miyoshi et al. (page 947). Cycles of severing and annealing may thus be more important than expected in creating a dynamic actin array.

The researchers had previously tracked the lifetimes of actin filaments in the lamellipodia of spreading Xenopus fibroblasts. They sought explanations for the range of lifetimes by looking at actin regulatory proteins such as CP. Surprisingly, the binding half life of CP in vivo was barely more than a second, compared with almost half an hour in vitro. The uncapped filaments appeared to resume their growth.

Although actin turnover is 20-fold slower than CP turnover, a further reduction in actin turnover by adding a cofilin inhibitor significantly reduced CP turnover. The authors suggest that cofilin-mediated filament severing may cause the dissociation of CP attached to a small actin oligomer. Such severing is presumably happening throughout the actin arrays, but with actin filaments at 1mM, reannealing would be a very favorable reaction.

Future work will focus on the factors that may be promoting CP dissociation and the in vivo cleavage activity of cofilin. Dendritic nucleation models of actin polymerization may also need to be revised, with CP apparently effecting a temporary and quantitative rather than qualitative change in actin polymerization. The new, more dynamic model might explain how motile cells can rapidly remodel an actin mesh to achieve a change in direction.

William A. Wells

wellsw{at}rockefeller.edu

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Actin turnover–dependent fast dissociation of capping protein in the dendritic nucleation actin network: evidence of frequent filament severing

Takushi Miyoshi, Takahiro Tsuji, Chiharu Higashida, Maud Hertzog, Akiko Fujita, Shuh Narumiya, Giorgio Scita, and Naoki Watanabe
J. Cell Biol. 2006 175: 947-955. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 820K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wells, W. A. Search for Related Content PubMed Articles by Wells, W. A. Related Collections Related Article Social Bookmarking                            What's this?