Interaction and localization of Necl-5 and PDGF receptor beta at the leading edges of moving NIH3T3 cells: Implications for directional cell movement.
It was previously shown that platelet-derived growth factor (PDGF) receptor physically and functionally interacts with integrin alpha(v)beta(3), effectively inducing cell movement. We previously showed that Necl-5, originally identified as a poliovirus receptor, interacts with integrin alpha(v)beta(3) and enhances its clustering and the formation of focal complexes at the leading edges of moving cells, resulting in an enhancement of cell movement. We showed here that Necl-5 additionally interacts with PDGF receptor in NIH3T3 cells and regulates the interaction between PDGF receptor and integrin alpha(v)beta(3), effectively inducing directional cell movement. PDGF receptor co-localized with Necl-5 and integrin alpha(v)beta(3) at peripheral ruffles over lamellipodia, which were formed at the leading edges of moving cells in response to PDGF, but not at the focal complexes under these ruffles, whereas Necl-5 and integrin alpha(v)beta(3) co-localized at these focal complexes. The clustering of these three molecules at peripheral ruffles required the activation of integrin alpha(v)beta(3) by vitronectin and the PDGF-induced activation of the small G protein Rac and subsequent re-organization of the actin cytoskeleton. These results indicate a key role of Necl-5 in directional cell movement by physically and functionally interacting with both integrin alpha(v)beta(3) and PDGF receptor.
Amano
Hisayuki
H
Department of Biochemistry and Molecular Biology, Faculty of Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan.
Ikeda
Wataru
W
Kawano
Satoshi
S
Kajita
Mihoko
M
Tamaru
Yoshiyuki
Y
Inoue
Naoya
N
Minami
Yukiko
Y
Yamada
Akio
A
Takai
Yoshimi
Y
D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology*; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation / Q000379:methods; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism; D051379:Mice; D041681:NIH 3T3 Cells; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D011554:Pseudopodia / Q000378:metabolism; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D020744:rac GTP-Binding Proteins / Q000378:metabolism
D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D039302:Integrin alphaVbeta3; D009363:Neoplasm Proteins; C476587:Taa1 protein, mouse; D020797:Receptor, Platelet-Derived Growth Factor beta; D020744:rac GTP-Binding Proteins