title: Protein 4.1R regulates cell migration and IQGAP1 recruitment to the leading edge.
abstract: In red blood cells, multifunctional protein 4.1R stabilizes the spectrin-actin network and anchors it to the plasma membrane. To contribute to the characterization of functional roles of 4.1R in nonerythroid cells, we have analyzed the participation of protein 4.1R in cell migration. The distribution of endogenous 4.1R is polarized towards the leading edge of migrating cells. Exogenous 4.1R isoforms containing a complete membrane-binding domain consistently localized to plasma membrane extensions enriched in F-actin. Silencing of 4.1R caused the loss of persistence of migration in subconfluent cells and of directional migration in cells moving into a wound. Coimmunoprecipitation and pull-down assays identified the scaffold protein IQGAP1 as a partner for protein 4.1R and showed that the 4.1R membrane-binding domain is involved in binding IQGAP1. Importantly, we show that protein 4.1R is necessary for the localization of IQGAP1 to the leading edge of cells migrating into a wound, whereas IQGAP1 is not required for protein 4.1R localization. Collectively, our results indicate a crucial role for protein 4.1R in cell migration and in the recruitment of the scaffold protein IQGAP1 to the cell front.
authors.affiliation: Centro de Biología Molecular Severo Ochoa and Departamento de Biología Molecular, Consejo Superior de Investigaciones Científicas and Universidad Autónoma de Madrid, Nicolás Cabrera 1, 28049-Madrid, Spain.
authors.forename: Ana
authors.initials: A
authors.lastname: Ruiz-Sáenz
authors.forename: Leonor
authors.initials: L
authors.lastname: Kremer
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Alonso
authors.forename: Jaime
authors.initials: J
authors.lastname: Millán
authors.forename: Isabel
authors.initials: I
authors.lastname: Correas
mesh_terms: D000818:Animals; D015153:Blotting, Western; D019556:COS Cells; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D047468:Immunoprecipitation; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D034622:RNA Interference; D020703:ras GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D003598:Cytoskeletal Proteins; C101203:IQ motif containing GTPase activating protein 1; D008565:Membrane Proteins; C028841:erythrocyte membrane band 4.1 protein; D020703:ras GTPase-Activating Proteins