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Synaptotagmin-mediated vesicle fusion regulates cell migration.
- Source :
-
Nature Immunology . Jun2010, Vol. 11 Issue 6, p495-502. 8p. 7 Graphs. - Publication Year :
- 2010
-
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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 15292908
- Volume :
- 11
- Issue :
- 6
- Database :
- Academic Search Index
- Journal :
- Nature Immunology
- Publication Type :
- Academic Journal
- Accession number :
- 50723336
- Full Text :
- https://doi.org/10.1038/ni.1878