Organelle selection determines agonist-specific Ca2+ signals in pancreatic acinar and beta cells |
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Authors: | Yamasaki Michiko Masgrau Roser Morgan Anthony J Churchill Grant C Patel Sandip Ashcroft Stephen J H Galione Antony |
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Affiliation: | Department of Pharmacology, University of Oxford, Mansfield Road, Oxford OX1 3QT, UK. |
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Abstract: | 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. |
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