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

doi:10.1038/ni.1878

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 journal › Article › peer-review

93 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 language	English (US)
Pages (from-to)	495-502
Number of pages	8
Journal	Nature Immunology
Volume	11
Issue number	6
DOIs	https://doi.org/10.1038/ni.1878
State	Published - Jun 2010
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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title = "Synaptotagmin-mediated vesicle fusion regulates cell migration",

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.",

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

year = "2010",

month = jun,

doi = "10.1038/ni.1878",

language = "English (US)",

volume = "11",

pages = "495--502",

journal = "Nature Immunology",

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AU - Colvin, Richard A.

AU - Means, Terry K.

AU - Diefenbach, Thomas J.

AU - Moita, Luis F.

AU - Friday, Robert P.

AU - Sever, Sanja

AU - Campanella, Gabriele S.V.

AU - Abrazinski, Tabitha

AU - Manice, Lindsay A.

AU - Moita, Catarina

AU - Andrews, Norma W.

AU - Wu, Dianqing

AU - Hacohen, Nir

AU - Luster, Andrew D.

PY - 2010/6

Y1 - 2010/6

N2 - 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.

AB - 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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Synaptotagmin-mediated vesicle fusion regulates cell migration

Abstract

ASJC Scopus subject areas

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