title: Identification of a novel Cdc42 GEF that is localized to the PAT-3-mediated adhesive structure.
abstract: In the model organism Caenorhabditis elegans, UNC-112 is colocalized with PAT-3/beta-integrin and is a critical protein in the formation of PAT-3-mediated adhesive structure in body-wall muscle cells. However, the signaling pathway downstream of PAT-3/UNC-112 is largely unknown. To clarify the signaling pathway from PAT-3/UNC-112 to the actin cytoskeleton, we searched for and identified a novel Dbl homology/pleckstrin homology (DH/PH) domain containing protein, UIG-1 (UNC-112-interacting guanine nucleotide exchange factor-1). UIG-1 was colocalized with UNC-112 at dense bodies in body-wall muscle cells. UIG-1 showed CDC-42-specific GEF activity in vitro and induced filopodia formation in NIH 3T3 cells. Depletion of CDC-42 or PAT-3 in the developmental stage, by RNAi, prevented the formation of continuous actin filament in body-wall muscle cells. Taken together, these results suggest that UIG-1 links a PAT-3/UNC-112 complex to the CDC-42 signaling pathway during muscle formation.
authors.affiliation: Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan.
authors.forename: Takao
authors.initials: T
authors.lastname: Hikita
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Qadota
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tsuboi
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Taya
authors.forename: Donald G
authors.initials: DG
authors.lastname: Moerman
authors.forename: Kozo
authors.initials: K
authors.lastname: Kaibuchi
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002522:Chlorocebus aethiops; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D039641:Integrin beta Chains / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism; D051379:Mice; D009132:Muscles / Q000166:cytology / Q000378:metabolism; D011485:Protein Binding; D011554:Pseudopodia / Q000378:metabolism; D015398:Signal Transduction; D000267:Tissue Adhesions; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D020662:Guanine Nucleotide Exchange Factors; D039641:Integrin beta Chains; D016023:Integrins; C504362:UIG-1 protein, C elegans; C411729:UNC-112 protein, C elegans; C093515:pat-3 protein, C elegans; D020764:cdc42 GTP-Binding Protein