Interaction and localization of Necl-5 and PDGF receptor β at the leading edges of moving NIH3T3 cells: Implications for directional cell movement

• Published in: Genes to cells : devoted to molecular & cellular mechanisms 2008-03, Vol.13 (3), p.269-284
• Main Authors: Amano, Hisayuki, Ikeda, Wataru, Kawano, Satoshi, Kajita, Mihoko, Tamaru, Yoshiyuki, Inoue, Naoya, Minami, Yukiko, Yamada, Akio, Takai, Yoshimi
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Neoplasm - genetics; Antigens, Neoplasm - metabolism; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Movement - physiology; Cells, Cultured; Chromatin Immunoprecipitation - methods; Humans; Integrin alphaVbeta3 - metabolism; Mice; Neoplasm Proteins - genetics; Neoplasm Proteins - metabolism; NIH 3T3 Cells; Protein Binding - physiology; Pseudopodia - metabolism; rac GTP-Binding Proteins - metabolism; Receptor, Platelet-Derived Growth Factor beta - genetics; Receptor, Platelet-Derived Growth Factor beta - metabolism
• ISSN: 1356-9597; 1365-2443
• DOI: 10.1111/j.1365-2443.2008.01167.x

It was previously shown that platelet-derived growth factor (PDGF) receptor physically and functionally interacts with integrin αvβ₃, effectively inducing cell movement. We previously showed that Necl-5, originally identified as a poliovirus receptor, interacts with integrin αvβ₃ 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 αvβ₃, effectively inducing directional cell movement. PDGF receptor co-localized with Necl-5 and integrin αvβ₃ 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 αvβ₃ co-localized at these focal complexes. The clustering of these three molecules at peripheral ruffles required the activation of integrin αvβ₃ 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 αvβ₃ and PDGF receptor.