title: Distinct roles of four gelsolin-like domains of Caenorhabditis elegans gelsolin-like protein-1 in actin filament severing, barbed end capping, and phosphoinositide binding.
abstract: Caenorhabditis elegans gelsolin-like protein-1 (GSNL-1) is a new member of the gelsolin family of actin regulatory proteins [Klaavuniemi, T., Yamashiro, S., and Ono, S. (2008) J. Biol. Chem. 283, 26071-26080]. It is an unconventional gelsolin-related protein with four gelsolin-like (G) domains (G1-G4), unlike typical gelsolin-related proteins with three or six G domains. GSNL-1 severs actin filaments and caps the barbed end in a calcium-dependent manner similar to that of gelsolin. In contrast, GSNL-1 has properties different from those of gelsolin in that it remains bound to F-actin and does not nucleate actin polymerization. To understand the mechanism by which GSNL-1 regulates actin dynamics, we investigated the domain-function relationship of GSNL-1 by analyzing activities of truncated forms of GSNL-1. G1 and the linker between G1 and G2 were sufficient for actin filament severing, whereas G1 and G2 were required for barbed end capping. The actin severing activity of GSNL-1 was inhibited by phosphatidylinositol 4,5-bisphosphate (PIP2), and a PIP2-sensitive domain was mapped to G1 and G2. At least two actin-binding sites were detected: a calcium-dependent G-actin-binding site in G1 and a calcium-independent G- and F-actin-binding site in G3 and G4. These results reveal both conserved and different utilization of G domains between C. elegans GSNL-1 and mammalian gelsolin for actin regulatory functions.
authors.affiliation: Department of Pathology and Department of Cell Biology, Emory University, Atlanta, Georgia 30322, USA.
authors.forename: Zhongmei
authors.initials: Z
authors.lastname: Liu
authors.forename: Tuula
authors.initials: T
authors.lastname: Klaavuniemi
authors.forename: Shoichiro
authors.initials: S
authors.lastname: Ono
mesh_terms: D051344:Actin Capping Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D008841:Actin Cytoskeleton / Q000378:metabolism*; D051339:Actin Depolymerizing Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D000199:Actins / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D018260:Gelsolin / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D052139:Intracellular Calcium-Sensing Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D008954:Models, Biological; D008970:Molecular Weight; D050505:Mutant Proteins / Q000737:chemistry / Q000378:metabolism; D010716:Phosphatidylinositols / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary / Q000502:physiology
chemical_list: D051344:Actin Capping Proteins; D051339:Actin Depolymerizing Factors; D000199:Actins; D029742:Caenorhabditis elegans Proteins; C532447:GSNL-1 protein, C elegans; D018260:Gelsolin; D052139:Intracellular Calcium-Sensing Proteins; D050505:Mutant Proteins; D010716:Phosphatidylinositols
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