Synaptotagmin-mediated vesicle fusion regulates cell migration.

Nature immunology 2010 Jun

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Chemokines and other chemoattractants direct leukocyte migration and are essential for the development and delivery of immune and inflammatory responses. To probe the molecular mechanisms that underlie chemoattractant-guided migration, we did an RNA-mediated interference screen that identified several members of the synaptotagmin family of calcium-sensing vesicle-fusion proteins as mediators of cell migration: SYT7 and SYTL5 were positive regulators of chemotaxis, whereas SYT2 was a negative regulator of chemotaxis. SYT7-deficient leukocytes showed less migration in vitro and in a gout model in vivo. Chemoattractant-induced calcium-dependent lysosomal fusion was impaired in SYT7-deficient neutrophils. In a chemokine gradient, SYT7-deficient lymphocytes accumulated lysosomes in their uropods and had impaired uropod release. Our data identify a molecular pathway required for chemotaxis that links chemoattractant-induced calcium flux to exocytosis and uropod release.

Citation

Richard A Colvin, Terry K Means, Thomas J Diefenbach, Luis F Moita, Robert P Friday, Sanja Sever, Gabriele S V Campanella, Tabitha Abrazinski, Lindsay A Manice, Catarina Moita, Norma W Andrews, Dianqing Wu, Nir Hacohen, Andrew D Luster. Synaptotagmin-mediated vesicle fusion regulates cell migration. Nature immunology. 2010 Jun;11(6):495-502