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Journal of Cell Science 115, 1591-1601 (2002)
© 2002 The Company of Biologists Limited

Research Article

Human CAP1 is a key factor in the recycling of cofilin and actin for rapid actin turnover

Kenji Moriyama* and Ichiro Yahara{ddagger}

Department of Cell Biology, The Tokyo Metropolitan Institute of Medical Science, Honkomagome, Bunkyo-ku, Tokyo 113-8613, Japan.
{ddagger} Present address: Medical & Biological Laboratories Co., Ltd., 1063-103, Ohara, Terasawaoka, Ina-city, 396-0002, Japan

* Author for correspondence (e-mail: moriyama{at}rinshoken.or.jp )

Cofilin-ADF (actin-depolymerizing factor) is an essential driver of actin-based motility. We discovered two proteins, p65 and p55, that are components of the actin-cofilin complex in a human HEK293 cell extract and identified p55 as CAP1/ASP56, a human homologue of yeast CAP/SRV2 (cyclase-associated protein). CAP is a bifunctional protein with an N-terminal domain that binds to Ras-responsive adenylyl cyclase and a C-terminal domain that inhibits actin polymerization. Surprisingly, we found that the N-terminal domain of CAP1, but not the C-terminal domain, is responsible for the interaction with the actin-cofilin complex. The N-terminal domain of CAP1 was also found to accelerate the depolymerization of F-actin at the pointed end, which was further enhanced in the presence of cofilin and/or the C-terminal domain of CAP1. Moreover, CAP1 and its C-terminal domain were observed to facilitate filament elongation at the barbed end and to stimulate ADP-ATP exchange on G-actin, a process that regenerates easily polymerizable G-actin. Although cofilin inhibited the nucleotide exchange on G-actin even in the presence of the C-terminal domain of CAP1, its N-terminal domain relieved this inhibition. Thus, CAP1 plays a key role in speeding up the turnover of actin filaments by effectively recycling cofilin and actin and through its effect on both ends of actin filament.

Key words: Actin, Adenylyl cyclase-associated protein, Cofilin/ADF, Cell motility, Actin-interacting protein 1


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