ATP-dependent regulation of actin monomer–filament equilibrium by cyclase-associated protein and ADF/cofilin

• Type of Material: Article
• Authors: Kazumi Nomura, Emory University; Shoichiro Ono, Emory University
• Language: English
• Date: 2013-07-15
• Publisher: Portland Press
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: ©The Authors Journal compilation ©2013 Biochemical Societ
• Final Published Version (URL): http://www.biochemj.org/bj/453/0249/bj4530249.htm
• Title of Journal or Parent Work: Biochemical Journal
• ISSN: 0264-6021
• Volume: 453
• Issue: 2
• Start Page: 249
• End Page: 259
• Grant/Funding Information: This work was supported by a grant from the National Institute of Health (R01 AR48615) to S. O.
• Keywords: nucleotide exchange; depolymerization; ADF/cofilin; cyclase-associated protein; Actin dynamics; polymerization
• Research Categories: Biology, Genetics; Biology, Cell; Health Sciences, Pathology

Abstract

SYNOPSIS Cyclase-associated protein (CAP) is a conserved regulator of actin filament dynamics. In the nematode Caenorhabditis elegans, CAS-1 is an isoform of CAP that is expressed in striated muscle and regulates sarcomeric actin assembly. Here, we report that CAS-2, a second CAP isoform in C. elegans, attenuates the actin-monomer-sequestering effect of actin depolymerizing factor (ADF)/cofilin to increase steady-state levels of actin filaments in an ATP-dependent manner. CAS-2 binds to actin monomers without a strong preference to either ATP- or ADP-actin. CAS-2 strongly enhances exchange of actin-bound nucleotides even in the presence of UNC-60A, which is a C. elegans ADF/cofilin that inhibits nucleotide exchange. UNC-60A induces depolymerization of actin filaments and sequesters actin monomers, whereas CAS-2 reverses the monomer-sequestering effect of UNC-60A in the presence of ATP but not in the presence of only ADP or absence of ATP or ADP. A 1:100 molar ratio of CAS-2 to UNC-60A is sufficient to increase actin filaments. CAS-2 has two independent actin-binding sites in the amino- and carboxyl-terminal halves, and the carboxyl-terminal half is necessary and sufficient for the observed activities of the full-length CAS-2. These results suggest that CAS-2 (CAP) and UNC-60A (ADF/cofilin) are important in ATP-dependent regulation of actin monomer-filament equilibrium.