title: Regulation of Integrin β 1 recycling to lipid rafts by Rab1a to promote cell migration.
abstract: Rab1a is a member of the Rab family of small GTPases with a well characterized function in the regulation of vesicle trafficking from the endoplasmic reticulum to the Golgi apparatus and within Golgi compartments. The integrin family heterodimeric transmembrane proteins serve as major receptors for extracellular matrix proteins, which play essential roles in cell adhesion and migration. Although effects on intracellular trafficking of integrins or other key cargos by Rab1a could influence cell migration, the regulatory mechanisms linking Rab1a to cell migration are not well understood. Here, we report identification of Rab1a as a novel regulator of cell migration using an unbiased RNAi screen targeting GTPases. Inhibition of Rab1a reduced integrin-mediated cell adhesion and spreading on fibronectins, reduced integrin β1 localization to lipid rafts, and decreased recycling of integrin β1 to the plasma membrane. Analysis of Rab1a effector molecules showed that p115 mediated Rab1a regulation of integrin recycling and lipid raft localization in cell migration. Taken together, these results suggest a novel function for Rab1a in the regulation of cell migration through controlling integrin β1 recycling and localization to lipid rafts via a specific downstream effector pathway.
authors.affiliation: Division of Molecular Medicine and Genetics, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: Chenran
authors.initials: C
authors.lastname: Wang
authors.forename: Youngdong
authors.initials: Y
authors.lastname: Yoo
authors.forename: Huaping
authors.initials: H
authors.lastname: Fan
authors.forename: Eunjung
authors.initials: E
authors.lastname: Kim
authors.forename: Kun-Liang
authors.initials: KL
authors.lastname: Guan
authors.forename: Jun-Lin
authors.initials: JL
authors.lastname: Guan
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000235:genetics / Q000502:physiology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D004330:Drosophila; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D034622:RNA Interference; D020761:rab1 GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019012:Integrin beta1; D020761:rab1 GTP-Binding Proteins