The role of cyclase-associated protein in regulating actin filament dynamics – more than a monomer-sequestration factor

Abstract

SummaryDynamic reorganization of the actin cytoskeleton is fundamental to a number of cell biological events. A variety of actin-regulatory proteins modulate polymerization and depolymerization of actin and contribute to actin cytoskeletal reorganization. Cyclase-associated protein (CAP) is a conserved actin-monomer-binding protein that has been studied for over 20 years. Early studies have shown that CAP sequesters actin monomers; recent studies, however, have revealed more active roles of CAP in actin filament dynamics. CAP enhances the recharging of actin monomers with ATP antagonistically to ADF/cofilin, and also promotes the severing of actin filaments in cooperation with ADF/cofilin. Self-oligomerization and binding to other proteins regulate activities and localization of CAP. CAP has crucial roles in cell signaling, development, vesicle trafficking, cell migration and muscle sarcomere assembly. This Commentary discusses the recent advances in our understanding of the functions of CAP and its implications as an important regulator of actin cytoskeletal dynamics, which are involved in various cellular activities.

Self-Incompatibility-Induced Programmed Cell Death in Field Poppy Pollen Involves Dramatic Acidification of the Incompatible Pollen Tube Cytosol

“…CAP sequesters actin monomers, prevents them from polymerization in vitro, and also, promotes the severing of actin filaments in association with ADF (Barrero et al, 2002;Chaudhry et al, 2007;Deeks et al, 2007;Ono, 2013). Plant CAP is likely to be a key regulator of actin dynamics using a mechanism unique to plants Ono, 2013).…”

“…CAP sequesters actin monomers, prevents them from polymerization in vitro, and also, promotes the severing of actin filaments in association with ADF (Barrero et al, 2002;Chaudhry et al, 2007;Deeks et al, 2007;Ono, 2013). Plant CAP is likely to be a key regulator of actin dynamics using a mechanism unique to plants Ono, 2013). The loss-of-function cap1 mutant in Arabidopsis has major defects in pollen germination and tube growth, with altered actin configuration consistent with a major role for CAP in regulating actin dynamics (Deeks et al, 2007).…”

Mammalian CAP (Cyclase-associated protein) in the world of cell migration

“…17,18 Most CAP homologs consist of three structural domains, namely the N terminus domain (NT), the C terminus domain (CT), and the proline-rich middle domain. 7,15 The NT is structurally less conserved compared with the CT and the middle domain and the G-actin sequestering capability was first mapped to the CT of both mammalian CAP1 and yeast CAP, although later a second G-actin binding site consisting of a WH2 (Wasp Homology 2) domain was also found. 7 All three domains of mammalian CAP1 and yeast CAP contribute to promoting actin filament turnover through interactions with cofilin as well as both Gand F-actin.…”

“…6 One G-actinsequestering protein is CAP (Cyclaseassociated protein), which is conserved in all eukaryotes, and has been studied for the past two decades. 7 CAP was first identified in yeast where it regulates both Ras/cAMP signaling and the actin cytoskeleton, but the Ras function is confined to yeast, accordingly, most subsequent studies have focused on its role in the actin cytoskeleton. [7][8][9][10] Mammalian CAP1 and yeast CAP both promote cofilin-driven actin filament turnover, which is believed to be a conserved feature among all CAP homologs based on the morphological phenotypes accompanying CAP perturbation, as well as the fact that expression of CAP homologs from other species rescues the actin phenotypes in CAP-knockout yeast.…”

“…[7][8][9][10] Mammalian CAP1 and yeast CAP both promote cofilin-driven actin filament turnover, which is believed to be a conserved feature among all CAP homologs based on the morphological phenotypes accompanying CAP perturbation, as well as the fact that expression of CAP homologs from other species rescues the actin phenotypes in CAP-knockout yeast. 7 7,15 CAP1 is more widely expressed and studied. The main focus of this commentary is on the role of mammalian CAP1 in cell migration, through its role in the actin filament dynamics and potential involvement in cell adhesion signaling.…”