Cyclase-associated protein interacts with actin filament barbed ends to promote depolymerization and formin displacement

被引:5
|
作者
Alimov, Nikita [1 ]
Hoeprich, Gregory J. [1 ]
Padrick, Shae B. [2 ]
Goode, Bruce L. [1 ]
机构
[1] Brandeis Univ, Rosenstiel Basic Med Sci Res Ctr, Dept Biol, Waltham, MA 02453 USA
[2] Drexel Univ, Dept Biochem & Mol Biol, Philadelphia, PA USA
关键词
ADP-ACTIN; F-ACTIN; STRUCTURAL BASIS; WH2; DOMAIN; ATP-ACTIN; SRV2/CAP COMPLEX; SKELETAL-MUSCLE; IN-VITRO; COFILIN; MECHANISM;
D O I
10.1016/j.jbc.2023.105367
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cyclase-associated protein (CAP) has emerged as a central player in cellular actin turnover, but its molecular mechanisms of action are not yet fully understood. Recent studies revealed that the N terminus of CAP interacts with the pointed ends of actin filaments to accelerate depolymerization in conjunction with cofilin. Here, we use in vitro microfluidics-assisted TIRF microscopy to show that the C terminus of CAP promotes depolymerization at the opposite (barbed) ends of actin filaments. In the absence of actin monomers, full-length mouse CAP1 and C-terminal halves of CAP1 (C-CAP1) and CAP2 (C-CAP2) accelerate barbed end depolymerization. Using mutagenesis and structural modeling, we show that these activities are mediated by the WH2 and CARP domains of CAP. In addition, we observe that CAP collaborates with profilin to accelerate barbed end depolymerization and that these effects depend on their direct interaction, providing the first known example of CAP-profilin collaborative effects in regulating actin. In the presence of actin monomers, CAP1 attenuates barbed end growth and promotes formin dissociation. Overall, these findings demonstrate that CAP uses distinct domains and mechanisms to interact with opposite ends of actin filaments and drive turnover. Further, they contribute to the emerging view of actin barbed ends as sites of dynamic molecular regulation, where numerous proteins compete and cooperate with each other to tune polymer dynamics, similar to the rich complexity seen at microtubule ends.
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收藏
页数:16
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