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

Alimov, Nikita; Hoeprich, Gregory J; Padrick, Shae B; Goode, Bruce L

Alimov, Nikita; Hoeprich, Gregory J; Padrick, Shae B; Goode, Bruce L.

Afiliación

Alimov N; Department of Biology, Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, Massachusetts, USA.
Hoeprich GJ; Department of Biology, Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, Massachusetts, USA.
Padrick SB; Department of Biochemistry and Molecular Biology, Drexel University, Philadelphia, Pennsylvania, USA.
Goode BL; Department of Biology, Rosenstiel Basic Medical Science Research Center, Brandeis University, Waltham, Massachusetts, USA. Electronic address: goode@brandeis.edu.

J Biol Chem ; 299(12): 105367, 2023 Dec.

Article en En | MEDLINE | ID: mdl-37863260

RESUMEN

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.

Asunto(s)

Citoesqueleto de Actina; Actinas; Proteínas del Citoesqueleto; Forminas; Proteínas de la Membrana; Animales; Ratones; Citoesqueleto de Actina/química; Citoesqueleto de Actina/metabolismo; Factores Despolimerizantes de la Actina/genética; Factores Despolimerizantes de la Actina/metabolismo; Actinas/química; Actinas/metabolismo; Forminas/metabolismo; Profilinas/metabolismo; Proteínas del Citoesqueleto/genética; Proteínas del Citoesqueleto/metabolismo; Proteínas de la Membrana/genética; Proteínas de la Membrana/metabolismo; Polimerizacion; Dominios Proteicos/genética; Modelos Moleculares; Estructura Terciaria de Proteína

Palabras clave

ADF; TIRF microscopy; actin; cofilin; cyclase-associated protein; turnover

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Citoesqueleto de Actina / Actinas / Proteínas del Citoesqueleto / Forminas / Proteínas de la Membrana Límite: Animals Idioma: En Revista: J Biol Chem Año: 2023 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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