Depletion of CAP1 in mammalian nonmuscle cells reduced cell motility by approximately 50% and transferrin uptake by 55% compared to wild-type cells, demonstrating its role in promoting rapid actin dynamics.
CAP1 is essential for proper subcellular localization and function of ADF/cofilin, promoting rapid actin dynamics in mammalian nonmuscle cells.
Absolute Event Rate: 27.6% vs 53.4%
p-value: p=<0.001
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 et al. (2004) studied this question. CAP1 siRNA knockdown vs. Wild-type / control siRNA was evaluated on Cell motility distance (µm) (p=<0.001). Depletion of CAP1 in mammalian nonmuscle cells reduced cell motility by approximately 50% and transferrin uptake by 55% compared to wild-type cells, demonstrating its role in promoting rapid actin dynamics.