期刊
NATURE IMMUNOLOGY
卷 11, 期 6, 页码 495-U60出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.1878
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资金
- US National Institutes of Health [R01 DK074449, R01 GM064625]
- Defense Advanced Research Projects Agency [W81XWH-04-C-0139]
- Fundacao Luso-Americana para o Desenvolvimento
- Fundacao para a Ciencia e a Tecnologia
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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