Endoplasmic reticulum Ca2+ is important for the proteolytic processing and intracellular transport of proinsulin in the pancreatic beta-cell.

摘要: The role of intracellular Ca2+ in the proteolytic processing and transport secretory granule proproteins was investigated by pulse-chase radiolabelling isolated rat islets Langerhans. conversion proinsulin inhibited depletion medium with EGTA blocking into cells Ca2+-channel antagonists verapamil, nifedipine NiCl2. Proinsulin also reduced endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin, indicating that process requires reticulum. This supported finding when depleted before or during pulse-labelling, but not after protein to post-endoplasmic-reticulum compartments. Similarly, inhibition reversed re-introduction around time radiolabelling, 15 min chase incubation. decreased maturation prohormone convertases PC1, PC2 carboxypeptidase H. Secretion experiments suggested rate extent granules were marginally depletion, whereas those markedly impeded. Inhibition thus simply related Ca2+-dependencies mature PC1 PC2, a requirement for their transfer granules. results suggest required enters pathway via