Dlg1 binds GKAP to control dynein association with microtubules, centrosome positioning, and cell polarity.
Centrosome positioning is crucial during cell division, cell differentiation, and for a wide range of cell-polarized functions including migration. In multicellular organisms, centrosome movement across the cytoplasm is thought to result from a balance of forces exerted by the microtubule-associated motor dynein. However, the mechanisms regulating dynein-mediated forces are still unknown. We show here that during wound-induced cell migration, the small G protein Cdc42 acts through the polarity protein Dlg1 to regulate the interaction of dynein with microtubules of the cell front. Dlg1 interacts with dynein via the scaffolding protein GKAP and together, Dlg1, GKAP, and dynein control microtubule dynamics and organization near the cell cortex and promote centrosome positioning. Our results suggest that, by modulating dynein interaction with leading edge microtubules, the evolutionary conserved proteins Dlg1 and GKAP control the forces operating on microtubules and play a fundamental role in centrosome positioning and cell polarity.
UMR144 Centre National de la Recherche Scientifique-Institut Curie, Paris, France.
Jean-Baptiste
JB
Manneville
Muguette
M
Jehanno
Sandrine
S
Etienne-Manneville
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001665:Binding Sites; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D018385:Centrosome / Q000378:metabolism*; D000074288:Discs Large Homolog 1 Protein; D004398:Dyneins / Q000378:metabolism*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D000074407:SAP90-PSD95 Associated Proteins; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C513314:DLG1 protein, human; C000614187:DLGAP1 protein, human; D000074288:Discs Large Homolog 1 Protein; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000074407:SAP90-PSD95 Associated Proteins; D004398:Dyneins; D020764:cdc42 GTP-Binding Protein