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- Title
Synaptotagmin-mediated vesicle fusion regulates cell migration.
- Authors
Colvin, Richard A; Means, Terry K; Diefenbach, Thomas J; Moita, Luis F; Friday, Robert P; Sever, Sanja; Campanella, Gabriele S V; Abrazinski, Tabitha; Manice, Lindsay A; Moita, Catarina; Andrews, Norma W; Wu, Dianqing; Hacohen, Nir; Luster, Andrew D
- Abstract
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.
- Subjects
CHEMOKINES; CELL migration; IMMUNE response; CHEMOTAXIS; LEUCOCYTE motility; UROPODA; EXOCYTOSIS
- Publication
Nature Immunology, 2010, Vol 11, Issue 6, p495
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni.1878