Cysteine-string proteins regulate exocytosis of insulin independent from transmembrane ion fluxes.
Cysteine-string proteins (Csps) are vesicle proteins involved in exocytosis of synaptic vesicles in Drosophila and modulation of presynaptic calcium influx. As both the contribution of calcium channel regulation to the role of Csp in exocytosis and a function of Csp outside the nervous system are unknown, we studied its function in endocrine exocytosis from large dense core vesicles (LDCVs) using insulin-secreting pancreatic beta-cells. Csps were expressed in primary and derived beta-cell lines on insulin-containing LDCVs. Suppression of Csp expression reduced not only depolarisation induced insulin release but also exocytosis in permeabilised cells directly stimulated by Ca2+. Thus, Csp is a secretory granule protein and is required for endocrine exocytosis independent of the modulation of transmembrane calcium fluxes.
Zhang
H
H
Département de Médecine Interne, Centre Médical Universitaire, Genève, Switzerland.
Kelley
W L
WL
Chamberlain
L H
LH
Burgoyne
R D
RD
Wollheim
C B
CB
Lang
J
J
D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D016373:DNA, Antisense / Q000096:biosynthesis; D005089:Exocytosis / Q000187:drug effects; D050956:HSP40 Heat-Shock Proteins; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007473:Ion Channels / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D051381:Rats; D013347:Subcellular Fractions / Q000378:metabolism; D014407:Tumor Cells, Cultured
D016373:DNA, Antisense; D050956:HSP40 Heat-Shock Proteins; D007328:Insulin; D007473:Ion Channels; D008565:Membrane Proteins; C088460:cysteine string protein