Identification of a novel Cdc42 GEF that is localized to the PAT-3-mediated adhesive structure.
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.
Hikita
Takao
T
Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa-ku, Nagoya, Aichi 466-8550, Japan.
Qadota
Hiroshi
H
Tsuboi
Daisuke
D
Taya
Shinichiro
S
Moerman
Donald G
DG
Kaibuchi
Kozo
K
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*
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