title: ARHGAP21 protein, a new partner of α-tubulin involved in cell-cell adhesion formation and essential for epithelial-mesenchymal transition.
abstract: Cell-cell adhesions and the cytoskeletons play important and coordinated roles in cell biology, including cell differentiation, development, and migration. Adhesion and cytoskeletal dynamics are regulated by Rho-GTPases. ARHGAP21 is a negative regulator of Rho-GTPases, particularly Cdc42. Here we assess the function of ARHGAP21 in cell-cell adhesion, cell migration, and scattering. We find that ARHGAP21 is localized in the nucleus, cytoplasm, or perinuclear region but is transiently redistributed to cell-cell junctions 4 h after initiation of cell-cell adhesion. ARHGAP21 interacts with Cdc42, and decreased Cdc42 activity coincides with the appearance of ARHGAP21 at the cell-cell junctions. Cells lacking ARHGAP21 expression show weaker cell-cell adhesions, increased cell migration, and a diminished ability to undergo hepatocyte growth factor-induced epithelial-mesenchymal transition (EMT). In addition, ARHGAP21 interacts with α-tubulin, and it is essential for α-tubulin acetylation in EMT. Our findings indicate that ARHGAP21 is a Rho-GAP involved in cell-cell junction remodeling and that ARHGAP21 affects migration and EMT through α-tubulin interaction and acetylation.
authors.affiliation: Hematology and Hemotherapy Center, University of Campinas/Hemocentro-Unicamp, Instituto Nacional de Ciência e Tecnologia do Sangue, Campinas, São Paulo, 13083-970, Brazil.
authors.forename: Karin S A
authors.initials: KS
authors.lastname: Barcellos
authors.forename: Carolina L
authors.initials: CL
authors.lastname: Bigarella
authors.forename: Mark V
authors.initials: MV
authors.lastname: Wagner
authors.forename: Karla P
authors.initials: KP
authors.lastname: Vieira
authors.forename: Mariana
authors.initials: M
authors.lastname: Lazarini
authors.forename: Peter R
authors.initials: PR
authors.lastname: Langford
authors.forename: João A
authors.initials: JA
authors.lastname: Machado-Neto
authors.forename: Steven G
authors.initials: SG
authors.lastname: Call
authors.forename: Davis M
authors.initials: DM
authors.lastname: Staley
authors.forename: Jarom Y
authors.initials: JY
authors.lastname: Chung
authors.forename: Marc D
authors.initials: MD
authors.lastname: Hansen
authors.forename: Sara T O
authors.initials: ST
authors.lastname: Saad
mesh_terms: D000107:Acetylation; D000818:Animals; D002448:Cell Adhesion; D002450:Cell Communication; D045744:Cell Line, Tumor; D002465:Cell Movement; D004285:Dogs; D058750:Epithelial-Mesenchymal Transition; D004848:Epithelium / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D061985:Madin Darby Canine Kidney Cells; D009362:Neoplasm Metastasis; D034622:RNA Interference; D013997:Time Factors; D014404:Tubulin / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: C459590:ARHGAP21 protein, human; D020690:GTPase-Activating Proteins; D014404:Tubulin; D020764:cdc42 GTP-Binding Protein