Article (Scientific journals)
Control of vesicle fusion by a tyrosine phosphatase.
Huynh, Huong; Bottini, Nunzio; Williams, Scott et al.
2004In Nature Cell Biology, 6 (9), p. 831-9
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Keywords :
Humans; Intracellular Membranes/physiology; Jurkat Cells; Membrane Fusion; Membrane Proteins/metabolism; Microscopy, Electron; N-Ethylmaleimide-Sensitive Proteins; Phosphorylation; Phosphotyrosine; Protein Binding; Protein Tyrosine Phosphatases/metabolism/physiology; Protein Tyrosine Phosphatases, Non-Receptor; Qa-SNARE Proteins; Secretory Vesicles/enzymology/physiology; Vesicular Transport Proteins/metabolism
Abstract :
[en] The tyrosine phosphatase PTP-MEG2 is targeted by its amino-terminal Sec14p homology domain to the membrane of secretory vesicles. There it regulates vesicle size by promoting homotypic vesicle fusion by a mechanism that requires its catalytic activity. Here, we identify N-ethylmaleimide-sensitive factor (NSF), a key regulator of vesicle fusion, as a substrate for PTP-MEG2. PTP-MEG2 reduced the phosphotyrosine content of NSF and co-localized with NSF and syntaxin 6 in intact cells. Furthermore, endogenous PTP-MEG2 co-immunoprecipitated with endogenous NSF. Phosphorylation of NSF at Tyr 83, as well as an acidic substitution at the same site, increased its ATPase activity and prevented alphaSNAP binding. Conversely, expression of a Y83F mutant of NSF caused spontaneous fusion events. Our results suggest that the molecular mechanism by which PTP-MEG2 promotes secretory vesicle fusion involves the local release of NSF from a tyrosine-phosphorylated, inactive state. This represents a novel mechanism for localized regulation of NSF and the first demonstrated role for a protein tyrosine phosphatase in the regulated secretory pathway.
Research center :
Program of Inflammation, Infectious and Inflammatory Disease Center, and Program of Signal Transduction, Cancer Center, The Burnham Institute
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Huynh, Huong
Bottini, Nunzio
Williams, Scott
Cherepanov, Vera
Musumeci, Lucia ;  Université de Liège - ULiège > GIGA-Research
Saito, Kan
Bruckner, Shane
Vachon, Eric
Wang, Xiaodong
Kruger, Joshua
Chow, Chung-Wai
Pellecchia, Maurizio
Monosov, Edvard
Greer, Peter A.
Trimble, William
Downey, Gregory P.
Mustelin, Tomas
More authors (7 more) Less
Language :
English
Title :
Control of vesicle fusion by a tyrosine phosphatase.
Publication date :
2004
Journal title :
Nature Cell Biology
ISSN :
1465-7392
eISSN :
1476-4679
Publisher :
Nature Publishing Group, United Kingdom
Volume :
6
Issue :
9
Pages :
831-9
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 07 January 2015

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