title: The interaction of mammalian Class C Vps with nSec-1/Munc18-a and syntaxin 1A regulates pre-synaptic release.
abstract: Membrane docking and fusion in neurons is a highly regulated process requiring the participation of a large number of SNAREs (soluble N-ethylmaleimide sensitive factor attachment protein receptors) and SNARE-interacting proteins. We found that mammalian Class C Vps protein complex associated specifically with nSec-1/Munc18-a, and syntaxin 1A both in vivo and in vitro. In contrast, VAMP2 and SNAP-25, other neuronal core complex proteins, did not interact. When co-transfected with the human growth hormone (hGH) reporter gene, mammalian Class C Vps proteins enhanced Ca2+-dependent exocytosis, which was abolished by the Ca2+-channel blocker nifedipine. In hippocampal primary cultures, the lentivirus-mediated overexpression of hVps18 increased asynchronous spontaneous synaptic release without changing mEPSCs. These results indicate that mammalian Class C Vps proteins are involved in the regulation of membrane docking and fusion through an interaction with neuronal specific SNARE molecules, nSec-1/Munc18-a and syntaxin 1A.
authors.affiliation: Department of Neurochemistry, National Institute of Neuroscience, NCNP, Kodaira, Tokyo 187-8502, Japan.
authors.forename: Bong Yoon
authors.initials: BY
authors.lastname: Kim
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Sahara
authors.forename: Akitsugu
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Eiki
authors.initials: E
authors.lastname: Kominami
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kohsaka
authors.forename: Chihiro
authors.initials: C
authors.lastname: Akazawa
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D051938:Munc18 Proteins / Q000378:metabolism*; D009474:Neurons / Q000502:physiology*; D017729:Presynaptic Terminals / Q000378:metabolism*; D025941:Protein Interaction Mapping; D051381:Rats; D009435:Synaptic Transmission / Q000502:physiology*; D050827:Syntaxin 1 / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D051938:Munc18 Proteins; C494213:Stx1a protein, rat; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins