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Generation of Specific Ca2+ Signals from Ca2+ Stores and Endocytosis by Differential Coupling to Messengers

Menteyne, Alexis, Burdakov, Anton, Charpentier, Gilles, Petersen, Ole Holger and Cancela, Jose-Manuel 2006. Generation of Specific Ca2+ Signals from Ca2+ Stores and Endocytosis by Differential Coupling to Messengers. Current Biology 16 (19) , pp. 1931-1937. 10.1016/j.cub.2006.07.070

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It remains unclear how different intracellular stores could interact and be recruited by Ca2+-releasing messengers to generate agonist-specific Ca2+ signatures. In addition, refilling of acidic stores such as lysosomes and secretory granules occurs through endocytosis, but this has never been investigated with regard to specific Ca2+ signatures. In pancreatic acinar cells, acetylcholine (ACh), cholecystokinin (CCK), and the messengers cyclic ADP-ribose (cADPR), nicotinic acid adenine dinucleotide phosphate (NAADP), and inositol 1,4,5-trisphosphate (IP3) evoke repetitive local Ca2+ spikes in the apical pole. Our work reveals that local Ca2+ spikes evoked by different agonists all require interaction of acid Ca2+ stores and the endoplasmic reticulum (ER), but in different proportions. CCK and ACh recruit Ca2+ from lysosomes and from zymogen granules through different mechanisms; CCK uses NAADP and cADPR, respectively, and ACh uses Ca2+ and IP3, respectively. Here, we provide pharmacological evidence demonstrating that endocytosis is crucial for the generation of repetitive local Ca2+ spikes evoked by the agonists and by NAADP and IP3. We find that cADPR-evoked repetitive local Ca2+ spikes are particularly dependent on the ER. We propose that multiple Ca2+-releasing messengers determine specific agonist-elicited Ca2+ signatures by controlling the balance among different acidic Ca2+ stores, endocytosis, and the ER.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Systems Immunity Research Institute (SIURI)
Publisher: Elsevier
ISSN: 0960-9822
Last Modified: 04 Jun 2017 06:31

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