Ca2+-dependent synaptotagmin binding to SNAP-25 is essential for Ca2+-triggered exocytosis.

Synaptotagmin is a proposed Ca2+ sensor on the vesicle for regulated exocytosis and exhibits Ca2+-dependent binding to phospholipids, syntaxin, and SNAP-25 in vitro, but the mechanism by which Ca2+ triggers membrane fusion is uncertain. Previous studies suggested that SNAP-25 plays a role in the Ca2+ regulation of secretion. We found ...
that synaptotagmins I and IX associate with SNAP-25 during Ca2+-dependent exocytosis in PC12 cells, and we identified C-terminal amino acids in SNAP-25 (Asp179, Asp186, Asp193) that are required for Ca2+-dependent synaptotagmin binding. Replacement of SNAP-25 in PC12 cells with SNAP-25 containing C-terminal Asp mutations led to a loss-of-function in regulated exocytosis at the Ca2+-dependent fusion step. These results indicate that the Ca2+-dependent interaction of synaptotagmin with SNAP-25 is essential for the Ca2+-dependent triggering of membrane fusion.
Mesh Terms:
Amino Acid Sequence, Animals, Aspartic Acid, Calcium, Calcium Signaling, Calcium-Binding Proteins, Central Nervous System, Exocytosis, Membrane Glycoproteins, Membrane Proteins, Mutation, Nerve Tissue Proteins, Neurotransmitter Agents, PC12 Cells, Presynaptic Terminals, Protein Binding, Protein Structure, Tertiary, Rats, SNARE Proteins, Synaptic Membranes, Synaptic Transmission, Synaptic Vesicles, Synaptosomal-Associated Protein 25, Synaptotagmins, Vesicular Transport Proteins
Neuron
Date: May. 16, 2002
Download Curated Data For This Publication
9339
Switch View:
  • Interactions 1