Regulation of protrusion, adhesion dynamics, and polarity by myosins IIA and IIB in migrating cells.
We have used isoform-specific RNA interference knockdowns to investigate the roles of myosin IIA (MIIA) and MIIB in the component processes that drive cell migration. Both isoforms reside outside of protrusions and act at a distance to regulate cell protrusion, signaling, and maturation of nascent adhesions. MIIA also controls the dynamics and size of adhesions in central regions of the cell and contributes to retraction and adhesion disassembly at the rear. In contrast, MIIB establishes front-back polarity and centrosome, Golgi, and nuclear orientation. Using ATPase- and contraction-deficient mutants of both MIIA and MIIB, we show a role for MIIB-dependent actin cross-linking in establishing front-back polarity. From these studies, MII emerges as a master regulator and integrator of cell migration. It mediates each of the major component processes that drive migration, e.g., polarization, protrusion, adhesion assembly and turnover, polarity, signaling, and tail retraction, and it integrates spatially separated processes.
Vicente-Manzanares
Miguel
M
Department of Cell Biology, University of Virginia, Charlottesville, VA 22908. mvz@virginia.edu
Zareno
Jessica
J
Whitmore
Leanna
L
Choi
Colin K
CK
Horwitz
Alan F
AF
D000199:Actins / Q000378:metabolism; D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D016466:CHO Cells; D002448:Cell Adhesion / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D016764:Cell Polarity; D006224:Cricetinae; D003412:Cricetulus; D024507:Nonmuscle Myosin Type IIA / Q000037:antagonists & inhibitors / Q000502:physiology*; D024501:Nonmuscle Myosin Type IIB / Q000037:antagonists & inhibitors / Q000502:physiology*; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000502:physiology; D034622:RNA Interference; D051381:Rats; D015398:Signal Transduction
D000199:Actins; D020033:Protein Isoforms; D000251:Adenosine Triphosphatases; D024507:Nonmuscle Myosin Type IIA; D024501:Nonmuscle Myosin Type IIB