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Publication : Synaptotagmin-mediated vesicle fusion regulates cell migration.

First Author  Colvin RA Year  2010
Journal  Nat Immunol Volume  11
Issue  6 Pages  495-502
PubMed ID  20473299 Mgi Jnum  J:160690
Mgi Id  MGI:4454947 Doi  10.1038/ni.1878
Citation  Colvin RA, et al. (2010) Synaptotagmin-mediated vesicle fusion regulates cell migration. Nat Immunol 11(6):495-502
abstractText  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.
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