title: Munc13 homology domain-1 in CAPS/UNC31 mediates SNARE binding required for priming vesicle exocytosis.
abstract: Neuropeptide and peptide hormone secretion from neural and endocrine cells occurs by Ca(2+)-triggered dense-core vesicle exocytosis. The membrane fusion machinery consisting of vesicle and plasma membrane SNARE proteins needs to be assembled for Ca(2+)-triggered vesicle exocytosis. The related Munc13 and CAPS/UNC31 proteins that prime vesicle exocytosis are proposed to promote SNARE complex assembly. CAPS binds SNARE proteins and stimulates SNARE complex formation on liposomes, but the relevance of SNARE binding to CAPS function in cells had not been determined. Here we identify a core SNARE-binding domain in CAPS as corresponding to Munc13 homology domain-1 (MHD1). CAPS lacking a single helix in MHD1 was unable to bind SNARE proteins or to support the Ca(2+)-triggered exocytosis of either docked or newly arrived dense-core vesicles. The results show that MHD1 is a SNARE-binding domain and that SNARE protein binding is essential for CAPS function in dense-core vesicle exocytosis.
authors.affiliation: Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA.
authors.forename: Chuenchanok
authors.initials: C
authors.lastname: Khodthong
authors.forename: Greg
authors.initials: G
authors.lastname: Kabachinski
authors.forename: Declan J
authors.initials: DJ
authors.lastname: James
authors.forename: Thomas F J
authors.initials: TF
authors.lastname: Martin
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002460:Cell Line; D022162:Cytoplasmic Vesicles / Q000378:metabolism*; D005089:Exocytosis; D006728:Hormones; D006801:Humans; D008081:Liposomes / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D011485:Protein Binding; D051381:Rats; D050600:SNARE Proteins / Q000378:metabolism*; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism
chemical_list: C059605:CAPS protein, human; D002135:Calcium-Binding Proteins; D006728:Hormones; D008081:Liposomes; D009419:Nerve Tissue Proteins; D050600:SNARE Proteins; C485548:UNC13B protein, human; D050988:Vesicle-Associated Membrane Protein 2; D002118:Calcium