Specificity and regulation of a synaptic vesicle docking complex

• Published in: Neuron (Cambridge, Mass.) Vol. 13; no. 2; pp. 353 - 361
• Main Authors: Pevsner, Jonathan, Hsu, Shu-Chan, Braun, Janice E.A., Calakos, Nicole, Ting, Anthony E., Bennett, Mark K., Scheller, Richard H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.1994
• Subjects: Amino Acid Sequence; Animals; Exocytosis; Fungal Proteins - physiology; In Vitro Techniques; Macromolecular Substances; Membrane Proteins - physiology; Molecular Sequence Data; Munc18 Proteins; Nerve Tissue Proteins - physiology; Peptides - chemistry; Protein Binding; R-SNARE Proteins; Rats; Recombinant Fusion Proteins; Synaptic Vesicles - physiology; Synaptosomal-Associated Protein 25; Vesicular Transport Proteins
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/0896-6273(94)90352-2

Synaptic vesicles are proposed to dock at the presynaptic plasma membrane through the interaction of two integral membrane proteins of synaptic vesicles, VAMP and synaptotagmin, and two plasma membrane proteins, syntaxin and SNAP-25. We have characterized the binding properties of these proteins and observed SNAP-25 potentiation of VAMP 2 binding to syntaxins la and 4 but not syntaxins 2 or 3. n-sec1, a neuron-specific syntaxin-binding protein, bound syntaxin with nanomolar affinity, forming a complex that is distinct from the previously identified 7S and 20S syntaxin-containing complexes. This suggests that syntaxin exists in at least three states: bound to n-sec1, in a 7S particle, and in a 20S particle. Recombinant n-secl inhibited VAMP or SNAP-25 binding to syntaxin. We propose that the specific associations of VAMP, SNAP-25, and syntaxin mediate vesicle docking and that a syntaxin/n-sec1 complex precedes and/or regulates formation of these complexes.