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How different extracellular stimuli can evoke different spatiotemporal Ca2+ signals is uncertain. We have elucidated a novel paradigm whereby different agonists use different Ca2+-storing organelles ("organelle selection") to evoke unique responses. Some agonists select the endoplasmic reticulum (ER), and others select lysosome-related (acidic) organelles, evoking spatial Ca2+ responses that mirror the organellar distribution. In pancreatic acinar cells, acetylcholine and bombesin exclusively select the ER Ca2+ store, whereas cholecystokinin additionally recruits a lysosome-related organelle. Similarly, in a pancreatic beta cell line MIN6, acetylcholine selects only the ER, whereas glucose mobilizes Ca2+ from a lysosome-related organelle. We also show that the key to organelle selection is the agonist-specific coupling messenger(s) such that the ER is selected by recruitment of inositol 1,4,5-trisphosphate (or cADP-ribose), whereas lysosome-related organelles are selected by NAADP.

Original publication

DOI

10.1074/jbc.M311088200

Type

Journal article

Journal

J Biol Chem

Publication Date

20/02/2004

Volume

279

Pages

7234 - 7240

Keywords

Acetylcholine, Animals, Bombesin, Calcium, Cell Line, Endoplasmic Reticulum, Enzyme Inhibitors, Islets of Langerhans, Lysosomes, Macrolides, Male, Mice, Models, Biological, NADP, Organelles, Pancreas, Signal Transduction, Thapsigargin, Time Factors, Ultraviolet Rays