title: The variable C-terminus of cysteine string proteins modulates exocytosis and protein-protein interactions.
abstract: Cysteine string proteins (Csps) are vesicle proteins involved in neurotransmission and hormone exocytosis. They are composed of distinct domains: a variable N-terminus, a J-domain followed by a linker region, a cysteine-rich string, and a C-terminus which diverges among isoforms. Their precise function and interactions are not fully understood. Using insulin exocytosis as a model, we show that the linker region and the C-terminus, but not the variable N-terminus, regulate overall secretion. Moreover, endogenous Csp1 binds in a calcium-dependent manner to monomeric VAMP2, and this interaction requires the C-terminus of Csp. The interaction is isoform specific as recombinant Csp1 binds VAMP1 and VAMP7, but not VAMP3. Cross-linking in permeabilized clonal beta-cells revealed homodimerization of Csp which is stimulated by Ca(2+) and again modulated by the variant C-terminus. Our data suggest that both interactions of Csp occur during exocytosis and may explain the effect of the variant C-terminus of this chaperon protein on peptide hormone secretion.
authors.affiliation: Institut Européen de Chimie et Biologie, Pôle Biologie Cellulaire et Moléculaire, JE 2390, 33607 Pessac/Bordeaux, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Boal
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Céline
authors.initials: C
authors.lastname: Tessier
authors.forename: Pier
authors.initials: P
authors.lastname: Scotti
authors.forename: Jochen
authors.initials: J
authors.lastname: Lang
mesh_terms: D002118:Calcium / Q000378:metabolism; D005089:Exocytosis / Q000502:physiology*; D050956:HSP40 Heat-Shock Proteins; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D011233:Precipitin Tests; D011485:Protein Binding / Q000502:physiology
chemical_list: D050956:HSP40 Heat-Shock Proteins; D007328:Insulin; D008565:Membrane Proteins; C088460:cysteine string protein; D002118:Calcium