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. |