Myosin IIA/IIB restrict adhesive and protrusive signaling to generate front-back polarity in migrating cells
| Autor: | Alexia I. Bachir, Miguel Vicente-Manzanares, Leanna Whitmore, Karen Newell-Litwa, Alan Rick Horwitz |
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| Rok vydání: | 2011 |
| Předmět: |
Dock180
macromolecular substances CHO Cells Biology Article 03 medical and health sciences 0302 clinical medicine Cricetulus Microtubule Cell Movement Cricetinae Cell polarity Animals Guanine Nucleotide Exchange Factors Phosphorylation Actin Research Articles 030304 developmental biology 0303 health sciences Nonmuscle Myosin Type IIB Cell adhesion molecule Nonmuscle Myosin Type IIA digestive oral and skin physiology Cell Polarity Cell Biology Adhesion Actomyosin Actin cytoskeleton 3. Good health Cell biology Actin Cytoskeleton Female Guanine nucleotide exchange factor Cell Adhesion Molecules 030217 neurology & neurosurgery Protein Binding Signal Transduction |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 |
| Popis: | Myosin IIA and IIB synergistically generate front–back polarity through their effects on actomyosin bundling formation and stability, and adhesion maturation, which are mediated by localized Rac GEF depletion. 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. |
| Databáze: | OpenAIRE |
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