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PMID:14993220

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Citation

Rao, SK, Huynh, C, Proux-Gillardeaux, V, Galli, T and Andrews, NW (2004) Identification of SNAREs involved in synaptotagmin VII-regulated lysosomal exocytosis. J. Biol. Chem. 279:20471-9

Abstract

Ca2+-regulated exocytosis of lysosomes has been recognized recently as a ubiquitous process, important for the repair of plasma membrane wounds. Lysosomal exocytosis is regulated by synaptotagmin VII, a member of the synaptotagmin family of Ca2+-binding proteins localized on lysosomes. Here we show that Ca2+-dependent interaction of the synaptotagmin VII C(2)A domain with SNAP-23 is facilitated by syntaxin 4. Specific interactions also occurred in cell lysates between the plasma membrane t-SNAREs SNAP-23 and syntaxin 4 and the lysosomal v-SNARE TI-VAMP/VAMP7. Following cytosolic Ca2+ elevation, SDS-resistant complexes containing SNAP-23, syntaxin 4, and TI-VAMP/VAMP7 were detected on membrane fractions. Lysosomal exocytosis was inhibited by the SNARE domains of syntaxin 4 and TI-VAMP/VAMP7 and by cleavage of SNAP-23 with botulinum neurotoxin E, thereby functionally implicating these SNAREs in Ca2+-regulated exocytosis of conventional lysosomes.

Links

PubMed Online version:10.1074/jbc.M400798200

Keywords

Animals; Antigens, CD/metabolism; Bacterial Proteins; Calcium/chemistry; Calcium/metabolism; Calcium-Binding Proteins; Carrier Proteins/metabolism; Cell Membrane/metabolism; Cell Survival; DNA/chemistry; Dose-Response Relationship, Drug; Electroporation; Exocytosis; Flow Cytometry; Lysosome-Associated Membrane Glycoproteins; Lysosomes/metabolism; Membrane Glycoproteins/metabolism; Membrane Glycoproteins/physiology; Membrane Proteins/metabolism; Microscopy, Fluorescence; Nerve Tissue Proteins/metabolism; Nerve Tissue Proteins/physiology; Precipitin Tests; Protein Binding; Protein Isoforms; Protein Structure, Tertiary; Qa-SNARE Proteins; Qb-SNARE Proteins; Qc-SNARE Proteins; R-SNARE Proteins; Rats; Recombinant Proteins/chemistry; SNARE Proteins; Streptolysins/pharmacology; Synaptotagmins; Vesicular Transport Proteins; beta-N-Acetylhexosaminidases/chemistry

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


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References

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