title: Activation of Rac by Asef2 promotes myosin II-dependent contractility to inhibit cell migration on type I collagen.
abstract: Non-muscle myosin II (MyoII) contractility is central to the regulation of numerous cellular processes, including migration. Rho is a well-characterized modulator of actomyosin contractility, but the function of other GTPases, such as Rac, in regulating contractility is currently not well understood. Here, we show that activation of Rac by the guanine nucleotide exchange factor Asef2 (also known as SPATA13) impairs migration on type I collagen through a MyoII-dependent mechanism that enhances contractility. Knockdown of endogenous Rac or treatment of cells with a Rac-specific inhibitor decreases the amount of active MyoII, as determined by serine 19 (S19) phosphorylation, and negates the Asef2-promoted increase in contractility. Moreover, treatment of cells with blebbistatin, which inhibits MyoII activity, abolishes the Asef2-mediated effect on migration. In addition, Asef2 slows the turnover of adhesions in protrusive regions of cells by promoting large mature adhesions, which has been linked to actomyosin contractility, with increased amounts of active β1 integrin. Hence, our data reveal a new role for Rac activation, promoted by Asef2, in modulating actomyosin contractility, which is important for regulating cell migration and adhesion dynamics.
authors.affiliation: Department of Biological Sciences and Vanderbilt Kennedy Center for Research on Human Development, Nashville, TN 37203, USA.
authors.forename: Léolène
authors.initials: L
authors.lastname: Jean
authors.forename: Devi
authors.initials: D
authors.lastname: Majumdar
authors.forename: Mingjian
authors.initials: M
authors.lastname: Shi
authors.forename: Louis E
authors.initials: LE
authors.lastname: Hinkle
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Diggins
authors.forename: Mingfang
authors.initials: M
authors.lastname: Ao
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Broussard
authors.forename: J Corey
authors.initials: JC
authors.lastname: Evans
authors.forename: David P
authors.initials: DP
authors.lastname: Choma
authors.forename: Donna J
authors.initials: DJ
authors.lastname: Webb
mesh_terms: D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D024042:Collagen Type I / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000502:physiology*; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism; D024462:Myosin Type II / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D020662:Guanine Nucleotide Exchange Factors; D019012:Integrin beta1; C525704:SPATA13 protein, human; D024462:Myosin Type II; D020764:cdc42 GTP-Binding Protein; D020744:rac GTP-Binding Proteins
keywords: Actomyosin; Adhesion dynamics; Asef2; Guanine nucleotide exchange factor; Rho GTPases; SPATA13; β1 integrin