Synaptotagmin-mediated vesicle fusion regulates cell migration

Richard A. Colvin, Terry K. Means, Thomas J. Diefenbach, Luis F. Moita, Robert P. Friday, Sanja Sever, Gabriele S.V. Campanella, Tabitha Abrazinski, Lindsay A. Manice, Catarina Moita, Norma W. Andrews, Dianqing Wu, Nir Hacohen, Andrew D. Luster

Research output: Contribution to journalArticlepeer-review

91 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)495-502
Number of pages8
JournalNature Immunology
Volume11
Issue number6
DOIs
StatePublished - Jun 2010
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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