title: Vimentin filaments regulate integrin-ligand interactions by binding to the cytoplasmic tail of integrin β3.
abstract: Vimentin, an intermediate filament protein induced during epithelial-to-mesenchymal transition, is known to regulate cell migration and invasion. However, it is still unclear how vimentin controls such behaviors. In this study, we aimed to find a new integrin regulator by investigating the H-Ras-mediated integrin suppression mechanism. Through a proteomic screen using the integrin β3 cytoplasmic tail protein, we found that vimentin might work as an effector of H-Ras signaling. H-Ras converted filamentous vimentin into aggregates near the nucleus, where no integrin binding can occur. In addition, an increase in the amount of vimentin filaments accessible to the integrin β3 tail enhanced talin-induced integrin binding to its ligands by inducing integrin clustering. In contrast, the vimentin head domain, which was found to bind directly to the integrin β3 tail and compete with endogenous vimentin filaments for integrin binding, induced nuclear accumulation of vimentin filaments and reduced the amount of integrin-ligand binding. Finally, we found that expression of the vimentin head domain can reduce cell migration and metastasis. From these data, we suggest that filamentous vimentin underneath the plasma membrane is involved in increasing integrin adhesiveness, and thus regulation of the vimentin-integrin interaction might control cell adhesion.
authors.affiliation: Department of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Jiyoon
authors.identifier: 0000-0003-4343-6333
authors.initials: J
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Korea University, Seoul 136-701, Republic of Korea School of Biological Sciences, Seoul National University, Seoul 151-747, Republic of Korea.
authors.forename: Chansik
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Eun Jin
authors.initials: EJ
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Brain Research Institute, and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Jungim
authors.initials: J
authors.lastname: Jang
authors.affiliation: Department of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: Se-Jong
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: Department of Life Sciences, Korea University, Seoul 136-701, Republic of Korea.
authors.forename: So Min
authors.initials: SM
authors.lastname: Kang
authors.affiliation: Department of Biological Sciences, Inha University, Incheon 402-720, Republic of Korea.
authors.forename: Moon Gyo
authors.initials: MG
authors.lastname: Kim
authors.affiliation: Department of Anatomy, Brain Research Institute, and Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Hosung
authors.initials: H
authors.lastname: Jung
authors.affiliation: School of Biological Sciences, Seoul National University, Seoul 151-747, Republic of Korea.
authors.forename: Dongeun
authors.initials: D
authors.lastname: Park
authors.affiliation: Department of Life Sciences, Korea University, Seoul 136-701, Republic of Korea chungho@korea.ac.kr.
authors.forename: Chungho
authors.initials: C
authors.lastname: Kim
mesh_terms: D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000235:genetics*; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002465:Cell Movement / Q000235:genetics; D006224:Cricetinae; D003412:Cricetulus; D003599:Cytoskeleton / Q000235:genetics / Q000378:metabolism*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics* / Q000378:metabolism; D008024:Ligands; D011485:Protein Binding; D060066:Protein Interaction Maps; D040901:Proteomics; D014746:Vimentin / Q000235:genetics* / Q000378:metabolism
chemical_list: D039661:Integrin beta3; D008024:Ligands; D014746:Vimentin
keywords: H-Ras; Integrin; Integrin activation; Talin; Vimentin