Wnt5a control of cell polarity and directional movement by polarized redistribution of adhesion receptors.
Mechanisms by which Wnt pathways integrate the organization of receptors, organelles, and cytoskeletal proteins to confer cell polarity and directional cell movement are incompletely understood. We show that acute responses to Wnt5a involve recruitment of actin, myosin IIB, Frizzled 3, and melanoma cell adhesion molecule into an intracellular structure in a melanoma cell line. In the presence of a chemokine gradient, this Wnt-mediated receptor-actin-myosin polarity (W-RAMP) structure accumulates asymmetrically at the cell periphery, where it triggers membrane contractility and nuclear movement in the direction of membrane retraction. The process requires endosome trafficking, is associated with multivesicular bodies, and is regulated by Wnt5a through the small guanosine triphosphatases Rab4 and RhoB. Thus, cell-autonomous mechanisms allow Wnt5a to control cell orientation, polarity, and directional movement in response to positional cues from chemokine gradients.
Witze
Eric S
ES
Department of Chemistry and Biochemistry, University of Colorado, Boulder, CO80309, USA.
Litman
Elizabeth S
ES
Argast
Gretchen M
GM
Moon
Randall T
RT
Ahn
Natalie G
NG
D000199:Actins / Q000378:metabolism; D000818:Animals; D051929:CD146 Antigen / Q000378:metabolism; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D016764:Cell Polarity; D054377:Chemokine CXCL12 / Q000378:metabolism; D002633:Chemotaxis; D011992:Endosomes / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D024501:Nonmuscle Myosin Type IIB / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014183:Transplantation, Heterologous; D051153:Wnt Proteins / Q000378:metabolism*; D000071818:Wnt-5a Protein; D020695:rab4 GTP-Binding Proteins / Q000378:metabolism; D020743:rhoB GTP-Binding Protein / Q000378:metabolism
D000199:Actins; D051929:CD146 Antigen; D054377:Chemokine CXCL12; D011518:Proto-Oncogene Proteins; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C438615:Wnt5a protein, mouse; D024501:Nonmuscle Myosin Type IIB; D020695:rab4 GTP-Binding Proteins; D020743:rhoB GTP-Binding Protein