Synaptotagmin 3 deficiency in T cells impairs recycling of the chemokine receptor CXCR4 and thereby inhibits CXCL12 chemokine-induced migration
Open Access
- 15 January 2007
- journal article
- Published by The Company of Biologists in Journal of Cell Science
- Vol. 120 (2), 219-228
- https://doi.org/10.1242/jcs.03328
Abstract
Synaptotagmins regulate vesicle trafficking and fusion of vesicles with membranes – processes that have been implicated in cell migration. We therefore hypothesized that synaptotagmins play a role in T-cell migration. Amongst synaptotagmins 1-11, we found synaptotagmin 3 (SYT3) to be the only one that is expressed in T cells. CXCR4-triggered migration was inhibited by antisense synaptotagmin 3 mRNA and by the isolated C2B domain, known to impair oligomerization of all synaptotagmins, but not by a C2B mutant that binds Ca2+ but does not block oligomerization. The C2B domain also blocked CXCR4-triggered actin polymerization and invasion. However, CXCR4-dependent adhesion in flow was not affected. Surprisingly, we found that little or no SYT3 is present near the plasma membrane but that it is mainly localized in multivesicular bodies, which also contained much of the CXCR4. Impaired SYT3 function blocked CXCR4 recycling and thus led to reduced surface levels of CXCR4. Migration was restored by overexpression of CXCR4. We conclude that STT3 is essential for CXCR4 recycling in T cells and thereby for the maintenance of high CXCR4 surface levels required for migration.Keywords
This publication has 46 references indexed in Scilit:
- Spatial Separation of HLA-DM/HLA-DR Interactions within MIIC and Phagosome-Induced Immune EscapeImmunity, 2005
- Exosomes: endosomal-derived vesicles shipping extracellular messagesCurrent Opinion in Cell Biology, 2004
- Plasma Membrane Repair Is Mediated by Ca2+-Regulated Exocytosis of LysosomesCell, 2001
- Synaptotagmin III/VII Isoforms Mediate Ca2+-induced Insulin Secretion in Pancreatic Islet β-CellsJournal of Biological Chemistry, 2000
- The C2b Domain of Synaptotagmin Is a Ca2+–Sensing Module Essential for ExocytosisThe Journal of cell biology, 2000
- The Biology of Chemokines and their ReceptorsAnnual Review of Immunology, 2000
- Rab11BP/Rabphilin-11, a Downstream Target of Rab11 Small G Protein Implicated in Vesicle RecyclingPublished by Elsevier BV ,1999
- Delineation of the Oligomerization, AP-2 Binding, and Synprint Binding Region of the C2B Domain of SynaptotagminPublished by Elsevier BV ,1998
- The synaptic vesicle protein synaptotagmin promotes formation of filopodia in fibroblastsNature, 1993
- Segregation of MHC class II molecules from MHC class I molecules in the Golgi complex for transport to lysosomal compartmentsNature, 1991