Synaptotagmin-mediated vesicle fusion regulates cell migration

被引：90

作者：

Colvin, Richard A. ^{[1
,2
]}

Means, Terry K. ^{[1
,2
]}

Diefenbach, Thomas J. ^{[3
]}

Moita, Luis F. ^{[1
,2
,4
]}

Friday, Robert P. ^{[1
,2
]}

Sever, Sanja ^{[5
]}

Campanella, Gabriele S. V. ^{[1
,2
]}

Abrazinski, Tabitha ^{[1
,2
]}

Manice, Lindsay A. ^{[1
,2
]}

Moita, Catarina ^{[1
,2
,4
]}

Andrews, Norma W. ^{[6
]}

Wu, Dianqing ^{[7
]}

Hacohen, Nir ^{[1
,2
,8
]}

Luster, Andrew D. ^{[1
,2
]}

机构：

[1] Massachusetts Gen Hosp, Div Rheumatol Allergy & Immunol, Ctr Immunol & Inflammatory Dis, Boston, MA 02114 USA

[2] Harvard Univ, Sch Med, Boston, MA USA

[3] MIT, Ragon Inst MGH, Boston, MA USA

[4] Univ Lisbon, Fac Med, Inst Mol Med, Cell Biol Immune Syst Unit, P-1699 Lisbon, Portugal

[5] Massachusetts Gen Hosp, Div Nephrol, Boston, MA 02114 USA

[6] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA

[7] Yale Univ, Sch Med, New Haven, CT USA

[8] Broad Inst, Cambridge, MA USA

来源：

NATURE IMMUNOLOGY | 2010年 / 11卷 / 06期

基金：

美国国家卫生研究院;

关键词：

CHEMOKINE RECEPTOR CXCR4; LENTIVIRAL RNAI LIBRARY; MYOSIN HEAVY-CHAIN; PHOSPHOINOSITIDE-3; KINASE; SIGNAL-TRANSDUCTION; NEUTROPHIL FUNCTION; LEADING LAMELLA; PLASMA-MEMBRANE; CHEMOTAXIS; FIBROBLASTS;

D O I：

10.1038/ni.1878

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：495 / U60

页数：10

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