CYSTEINE-STRING PROTEINS REGULATE EXOCYTOSIS OF INSULIN-INDEPENDENT FROM TRANSMEMBRANE ION FLUXES

Cysteine-string proteins (Csps) are vesicle proteins involved in exocy tosis of synaptic vesicles in Drosophila and modulation of presynaptic calcium influx. As both the contribution of calcium channel regulatio n to the role of Csp in exocytosis and a function of Csp outside the n ervous system are unknown, we studied its function in endocrine exocyt osis from large dense core vesicles (LDCVs) using insulin-secreting pa ncreatic beta-cells. Csps were expressed in primary and derived beta-c ell lines on insulin-containing LDCVs. Suppression of Csp expression r educed not only depolarisation induced insulin release but also exocyt osis in permeabilised cells directly stimulated by Ca2+. Thus, Csp is a secretory granule protein and is required for endocrine exocytosis i ndependent of the modulation of transmembrane calcium fluxes. (C) 1998 Federation of European Biochemical Societies.