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¹ Department of Biochemistry and Molecular Biology, Faculty of Medicine, Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan
² KAN Research Institute Inc., Kobe MI R&D Center, Kobe 650-0047, Japan
³ Department of Biochemistry and Molecular Biology, Faculty of Medicine, Division of Molecular and Cellular Biology, Graduate School of Medicine, Kobe University, Kobe, 650-0017, Japan

It was previously shown that platelet-derived growth factor (PDGF) receptor physically and functionally interacts with integrin _vβ₃, effectively inducing cell movement. We previously showed that Necl-5, originally identified as a poliovirus receptor, interacts with integrin _vβ₃ 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 _vβ₃, effectively inducing directional cell movement. PDGF receptor co-localized with Necl-5 and integrin _vβ₃ 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 _vβ₃ co-localized at these focal complexes. The clustering of these three molecules at peripheral ruffles required the activation of integrin _vβ₃ 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 _vβ₃ and PDGF receptor.

^* Correspondence: E-mail: ytakai{at}med.kobe-u.ac.jp

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				M. Takahashi, Y. Rikitake, Y. Nagamatsu, T. Hara, W. Ikeda, K.-i. Hirata, and Y. Takai Sequential activation of Rap1 and Rac1 small G proteins by PDGF locally at leading edges of NIH3T3 cells. Genes Cells, June 1, 2008; 13(6): 549 - 569. [Abstract] [Full Text] [PDF]