Cyclase-associated protein 1 (CAP1) promotes cofilin-induced actin dynamics in mammalian nonmuscle cells.
Cyclase-associated proteins (CAPs) are highly conserved actin monomer binding proteins present in all eukaryotes. However, the mechanism by which CAPs contribute to actin dynamics has been elusive. In mammals, the situation is further complicated by the presence of two CAP isoforms whose differences have not been characterized. Here, we show that CAP1 is widely expressed in mouse nonmuscle cells, whereas CAP2 is the predominant isoform in developing striated muscles. In cultured NIH3T3 and B16F1 cells, CAP1 is a highly abundant protein that colocalizes with cofilin-1 to dynamic regions of the cortical actin cytoskeleton. Analysis of CAP1 knockdown cells demonstrated that this protein promotes rapid actin filament depolymerization and is important for cell morphology, migration, and endocytosis. Interestingly, depletion of CAP1 leads to an accumulation of cofilin-1 into abnormal cytoplasmic aggregates and to similar cytoskeletal defects to those seen in cofilin-1 knockdown cells, demonstrating that CAP1 is required for proper subcellular localization and function of ADF/cofilin. Together, these data provide the first direct in vivo evidence that CAP promotes rapid actin dynamics in conjunction with ADF/cofilin and is required for several central cellular processes in mammals.
Bertling
Enni
E
Program in Cellular Biotechnology, Institute of Biotechnology, 00014 University of Helsinki, Finland.
Hotulainen
Pirta
P
Mattila
Pieta K
PK
Matilainen
Tanja
T
Salminen
Marjo
M
Lappalainen
Pekka
P
D008841:Actin Cytoskeleton / Q000378:metabolism*; D051339:Actin Depolymerizing Factors; D000199:Actins / Q000032:analysis / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051345:Destrin; D004705:Endocytosis / Q000502:physiology; D015870:Gene Expression; D020868:Gene Silencing; D017403:In Situ Hybridization; D051379:Mice; D008840:Microfilament Proteins / Q000032:analysis / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D034622:RNA Interference; D012333:RNA, Messenger / Q000032:analysis; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D051339:Actin Depolymerizing Factors; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C090135:Cap2 protein, S cerevisiae; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D051345:Destrin; C495825:Dstn protein, mouse; D008840:Microfilament Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C073751:SRV2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins