title: Socius is a novel Rnd GTPase-interacting protein involved in disassembly of actin stress fibers.
abstract: Rho family small GTPases are key regulators of the actin cytoskeleton in various cell types. The Rnd proteins, Rnd1, Rnd2, and Rnd3/RhoE, have been recently identified as new members of the Rho family of GTPases, and expression of Rnd1 or Rnd3 in fibroblasts causes the disassembly of actin stress fibers and the retraction of the cell body to produce extensively branching cellular processes. Here we have performed a yeast two-hybrid screening by using Rnd1 as bait and identified a novel protein that specifically binds to Rnd GTPases. We named this protein Socius. Socius directly binds to Rnd GTPases through its COOH-terminal region. When transfected into COS-7 cells, Socius is translocated to the cell periphery in response to Rnd1 and Rnd3 and colocalized with the GTPases. While expression of wild-type Socius in Swiss 3T3 fibroblasts has little effect on the actin cytoskeleton, the expression of a membrane-targeted form of Socius, containing a COOH-terminal farnesylation motif (Socius-CAAX), induces a dramatic loss of stress fibers. The inhibitory effect of Socius-CAAX on stress fiber formation is enhanced by truncation of its NH(2) terminus. On the other hand, the expression of Socius-CAAX or its NH(2) terminus-truncated form suppresses the Rnd-induced retraction of the cell body and the production of extensively branching cellular processes, although the disassembly of stress fibers is observed. We propose that Socius participates in the Rnd GTPase-induced signal transduction pathways, leading to reorganization of the actin cytoskeleton.
authors.affiliation: Laboratory of Molecular Neurobiology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan. hirokato@pharm.kyoto-u.ac.jp
authors.forename: Hironori
authors.initials: H
authors.lastname: Katoh
authors.forename: Amane
authors.initials: A
authors.lastname: Harada
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Mori
authors.forename: Manabu
authors.initials: M
authors.lastname: Negishi
mesh_terms: D016475:3T3 Cells; D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D000951:Antigens, Neoplasm; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D048429:Cell Size; D003599:Cytoskeleton / Q000378:metabolism; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D021381:Protein Transport; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D022502:Stress Fibers / Q000378:metabolism*; D020798:Two-Hybrid System Techniques; D020741:rho GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D000199:Actins; D000951:Antigens, Neoplasm; D002352:Carrier Proteins; D012333:RNA, Messenger; C454440:UBXN11 protein, human; D020741:rho GTP-Binding Proteins