Mechanism and biological role of profilin-Srv2/CAP interaction

SummaryAssembly of contractile apparatuses in striated muscle requires precisely regulated reorganization of the actin cytoskeletal proteins into sarcomeric organization. Regulation of actin filament dynamics is one of the essential processes of myofibril assembly, but the mechanism of actin regulation in striated muscle is not clearly understood. Actin depolymerizing factor (ADF)/cofilin is a key enhancer of actin filament dynamics in striated muscle in both vertebrates and nematodes. Here, we report that CAS-1, a cyclase-associated protein in Caenorhabditis elegans, promotes ADF/cofilin-dependent actin filament turnover in vitro and is required for sarcomeric actin organization in striated muscle. CAS-1 is predominantly expressed in striated muscle from embryos to adults. In vitro, CAS-1 binds to actin monomers and enhances exchange of actin-bound ATP/ADP even in the presence of UNC-60B, a muscle-specific ADF/cofilin that inhibits the nucleotide exchange. As a result, CAS-1 and UNC-60B cooperatively enhance actin filament turnover. The two proteins also cooperate to shorten actin filaments. A cas-1 mutation is homozygous lethal with defects in sarcomeric actin organization. cas-1-mutant embryos and worms have aggregates of actin in muscle cells, and UNC-60B is mislocalized to the aggregates. These results provide genetic and biochemical evidence that cyclase-associated protein is a critical regulator of sarcomeric actin organization in striated muscle.

Section: Resultsmentioning

confidence: 99%

CAS-1, a C. elegans cyclase-associated protein, is required for sarcomeric actin assembly in striated muscle

Nomura

Ono

2012

“…In addition, the cof1-19 srv2 mutation is lethal. Srv2 functions as a mediator to transfer actin subunits from cofilin to profilin and facilitates actin recycling in cells (Balcer et al, 2003;Bertling et al, 2007). Thus, cof1-19 must affect more than the association of Aip1 with actin patches.…”

Section: Actin-patch Dynamics: Cofilin Is More Important Than Aip1mentioning

confidence: 99%

“…The cof1-5 mutant protein is biochemically defective in Srv2 protein interaction (Quintero-Monzon et al, 2009). Srv2 mediates transfer of actin monomers produced by cofilin depolymerization to profilin, to facilitate actin cycling in cells (Balcer et al, 2003;Bertling et al, 2007;Mattila et al, 2004;Quintero-Monzon et al, 2009). In addition, cof1-19 mutant protein has been shown, biochemically, to have G-actin-binding defects (Ojala et al, 2001), and cof1-19 has a genetic interaction with SRV2 and the gene encoding profilin (Balcer et al, 2003).…”

Section: The Essential and Diverse Roles Of Cofilin In Yeast Actinpatmentioning

confidence: 99%

Overlapping and distinct functions for cofilin, coronin and Aip1 in actin dynamics in vivo

Lin

Galletta

Sept

et al. 2010

SummaryActin-filament disassembly is crucial for actin-based motility, to control filament network architecture and to regenerate subunits for assembly. Here, we examined the roles of three actin cytoskeletal proteins, coronin, cofilin and Aip1, which have been suggested to combine in various ways to control actin dynamics by promoting or regulating disassembly. We studied their functions during the endocytosis process in budding yeast, where actin-filament dynamics at the cortical actin 'patch' contribute to the formation and movement of endocytic vesicles. We found that all three proteins were recruited during the late phase of the life of the actin patch. They all arrived at the same time, when actin and other actin-associated proteins were leaving the patch. Cofilin point mutations influenced the localization of coronin and Aip1, but the complete loss of coronin had no effect on localization of cofilin or Aip1. Using quantitative patch motion analysis and comparing mutant alleles, the phenotypes for mutations of the three genes showed some commonalities, but also some striking differences. Cofilin was clearly the most important; it displayed the most severe mutant phenotypes affecting actin-patch assembly and movement. Together, the results suggest that all three proteins work together to promote actin disassembly, but not in a simple way, and not with equal importance.

“…The binding of wild-type ABBA and ABBA 274-715 -mutWH2 protein fragments to NBD-labelled actin was carried out as described (Bertling et al, 2007). In the actin-bundling assay, samples were sedimented at 17,000 g for 30 minutes and the assay was otherwise carried out as described (Mattila et al, 2003).…”

Section: Actin Assaysmentioning

confidence: 99%

ABBA regulates plasma-membrane and actin dynamics to promote radial glia extension

Saarikangas

Hakanen

Mattila

et al. 2008

Self Cite

Radial glia play key roles in neuronal migration, axon guidance, and neurogenesis during development of the central nervous system. However, the molecular mechanisms regulating growth and morphology of these extended cells are unknown. We show that ABBA, a novel member of the IRSp53-MIM protein family, is enriched in different types of radial glia. ABBA binds ATPactin monomers with high affinity and deforms PtdIns(4,5)P 2 -rich membranes in vitro through its WH2 and IM domains, respectively. In radial-glia-like C6-R cells, ABBA localises to the interface between the actin cytoskeleton and plasma membrane, and its depletion by RNAi led to defects in lamellipodial dynamics and process extension. Together, this study identifies ABBA as a novel regulator of actin and plasma membrane dynamics in radial glial cells, and provides evidence that membrane binding and deformation activity is critical for the cellular functions of IRSp53-MIM-ABBA family proteins. Supplementary material available online at