title: Myosin IIA/IIB restrict adhesive and protrusive signaling to generate front-back polarity in migrating cells.
abstract: Migratory front-back polarity emerges from the cooperative effect of myosin IIA (MIIA) and IIB (MIIB) on adhesive signaling. We demonstrate here that, during polarization, MIIA and MIIB coordinately promote localized actomyosin bundling, which generates large, stable adhesions that do not signal to Rac and thereby form the cell rear. MIIA formed dynamic actomyosin proto-bundles that mark the cell rear during spreading; it also bound to actin filament bundles associated with initial adhesion maturation in protrusions. Subsequent incorporation of MIIB stabilized the adhesions and actomyosin filaments with which it associated and formed a stable, extended rear. These adhesions did not turn over and no longer signal to Rac. Microtubules fine-tuned the polarity by positioning the front opposite the MIIA/MIIB-specified rear. Decreased Rac signaling in the vicinity of the MIIA/MIIB-stabilized proto-bundles and adhesions was accompanied by the loss of Rac guanine nucleotide exchange factor (GEFs), like βPIX and DOCK180, and by inhibited phosphorylation of key residues on adhesion proteins that recruit and activate Rac GEFs. These observations lead to a model for front-back polarity through local GEF depletion.
authors.affiliation: Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA. miguel.vicente@uam.es
authors.forename: Miguel
authors.initials: M
authors.lastname: Vicente-Manzanares
authors.forename: Karen
authors.initials: K
authors.lastname: Newell-Litwa
authors.forename: Alexia I
authors.initials: AI
authors.lastname: Bachir
authors.forename: Leanna A
authors.initials: LA
authors.lastname: Whitmore
authors.forename: Alan Rick
authors.initials: AR
authors.lastname: Horwitz
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002465:Cell Movement / Q000502:physiology; D016764:Cell Polarity; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism; D024507:Nonmuscle Myosin Type IIA / Q000378:metabolism*; D024501:Nonmuscle Myosin Type IIB / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D015398:Signal Transduction
chemical_list: D015815:Cell Adhesion Molecules; D020662:Guanine Nucleotide Exchange Factors; D000205:Actomyosin; D024507:Nonmuscle Myosin Type IIA; D024501:Nonmuscle Myosin Type IIB