title: Necl-5/poliovirus receptor interacts in cis with integrin alphaVbeta3 and regulates its clustering and focal complex formation.
abstract: Integrin alphavbeta3, which forms focal complexes at leading edges in moving cells, is up-regulated in cancer cells and so is implicated in their invasiveness. Necl-5, originally identified as a poliovirus receptor and also up-regulated in cancer cells, colocalizes with integrin alphavbeta3 at leading edges in moving cells and enhances growth factor-induced cell movement. Here, we show that Necl-5 interacts directly, in cis, with integrin alphavbeta3, and enhances integrin alphavbeta3 clustering and focal complex formation at leading edges in NIH3T3 cells. The extracellular region of Necl-5, but not the cytoplasmic region, is necessary for its interaction with integrin alphavbeta3; however, both regions are necessary for its action. An interaction between integrin alphavbeta3 and vitronectin and PDGF-induced activation of Rac are also necessary for integrin alphavbeta3 clustering. The interaction between Necl-5 and integrin alphavbeta3 enhances PDGF-induced Rac activation, facilitating integrin alphavbeta3 clustering presumably in a feedback amplification manner. Thus, Necl-5 has a critical role in integrin alphavbeta3 clustering and focal complex formation.
authors: Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka, Japan; Surgery and Clinical Oncology, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka, Japan.
authors: Yukiko
authors: Y
authors: Minami
authors: Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka, Japan.
authors: Wataru
authors: W
authors: Ikeda
authors: Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka, Japan.
authors: Mihoko
authors: M
authors: Kajita
authors: Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka, Japan; Surgery and Clinical Oncology, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka, Japan.
authors: Tsutomu
authors: T
authors: Fujito
authors: Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka, Japan.
authors: Hisayuki
authors: H
authors: Amano
authors: Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka, Japan.
authors: Yoshiyuki
authors: Y
authors: Tamaru
authors: Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka, Japan.
authors: Kaori
authors: K
authors: Kuramitsu
authors: Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka, Japan.
authors: Yasuhisa
authors: Y
authors: Sakamoto
authors: Surgery and Clinical Oncology, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka, Japan.
authors: Morito
authors: M
authors: Monden
authors: Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Osaka, Japan. Electronic address: ytakai@molbio.med.osaka-u.ac.jp.
authors: Yoshimi
authors: Y
authors: Takai
mesh_terms: D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008856:Microscopy, Fluorescence; D041681:NIH 3T3 Cells; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000378:metabolism; D011991:Receptors, Virus / Q000378:metabolism / Q000502:physiology*
chemical_list: D039302:Integrin alphaVbeta3; D008565:Membrane Proteins; D010982:Platelet-Derived Growth Factor; D034741:RNA, Small Interfering; D011991:Receptors, Virus; C066100:poliovirus receptor