title: βArrestin1 regulates the guanine nucleotide exchange factor RasGRF2 expression and the small GTPase Rac-mediated formation of membrane protrusion and cell motility.
abstract: βArrestin proteins shuttle between the cytosol and nucleus and have been shown to regulate G protein-coupled receptor signaling, actin remodeling, and gene expression. Here, we tested the hypothesis that βarrestin1 regulates actin remodeling and cell migration through the small GTPase Rac. Depletion of βarrestin1 promotes Rac activation, leading to the formation of multipolar protrusions and increased cell circularity, and overexpression of a dominant negative form of Rac reverses these morphological changes. Small interfering RNA library screen identifies RasGRF2 as a target of βarrestin1. RasGRF2 gene and protein expression levels are elevated following depletion of βarrestin1, and the consequent activation of Rac results in dephosphorylation of cofilin that can promote actin polymerization and formation of multipolar protrusions, thereby retarding cell migration and invasion. Together, these results suggest that βarrestin1 regulates rasgrf2 gene expression and Rac activation to affect membrane protrusion and cell migration and invasion.
authors.affiliation: From the Department of Anatomy and Cell Biology, University of Florida College of Medicine, Gainesville, Florida 32610.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Ma
authors.forename: Laura
authors.initials: L
authors.lastname: Espana-Serrano
authors.forename: Wan-ju
authors.initials: WJ
authors.lastname: Kim
authors.forename: Hamsa
authors.initials: H
authors.lastname: Thayele Purayil
authors.forename: Zhongzhen
authors.initials: Z
authors.lastname: Nie
authors.forename: Yehia
authors.initials: Y
authors.lastname: Daaka
mesh_terms: D000818:Animals; D019390:Arrestins / Q000235:genetics / Q000378:metabolism*; D021961:Cell Membrane Structures / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D010766:Phosphorylation / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D000071557:beta-Arrestins; D020663:ras Guanine Nucleotide Exchange Factors / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D019390:Arrestins; C504490:RASGRF2 protein, human; C504491:Rasgrf2 protein, mouse; D000071557:beta-Arrestins; D020663:ras Guanine Nucleotide Exchange Factors; D051057:Proto-Oncogene Proteins c-akt
keywords: Actin; Arrestin; Cell Migration; G Protein-coupled Receptors (GPCR); Guanine Nucleotide Exchange Factor (GEF); Protrusion; Rac