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InsP3 receptors and Orai channels in pancreatic acinar cells: co-localization and its consequences

Lur, Gyorgy, Sherwood, Mark, Ebisui, Etsuko, Haynes, Lee, Feske, Stefan, Sutton, Robert, Burgoyne, Robert, Mikoshiba, Katsuhiko, Petersen, Ole Holger and Tepikin, Alexei 2011. InsP3 receptors and Orai channels in pancreatic acinar cells: co-localization and its consequences. Biochemical Journal 436 (2) , pp. 231-239. 10.1042/BJ20110083

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Orai1 proteins have been recently identified as subunits of SOCE (store-operated Ca2+ entry) channels. In primary isolated PACs (pancreatic acinar cells), Orai1 showed remarkable co-localization and co-immunoprecipitation with all three subtypes of IP3Rs (InsP3 receptors). The co-localization between Orai1 and IP3Rs was restricted to the apical part of PACs. Neither co-localization nor co-immunoprecipitation was affected by Ca2+ store depletion. Importantly we also characterized Orai1 in basal and lateral membranes of PACs. The basal and lateral membranes of PACs have been shown previously to accumulate STIM1 (stromal interaction molecule 1) puncta as a result of Ca2+ store depletion. We therefore conclude that these polarized secretory cells contain two pools of Orai1: an apical pool that interacts with IP3Rs and a basolateral pool that interacts with STIM1 following the Ca2+ store depletion. Experiments on IP3R knockout animals demonstrated that the apical Orai1 localization does not require IP3Rs and that IP3Rs are not necessary for the activation of SOCE. However, the InsP3-releasing secretagogue ACh (acetylcholine) produced a negative modulatory effect on SOCE, suggesting that activated IP3Rs could have an inhibitory effect on this Ca2+ entry mechanism.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Systems Immunity Research Institute (SIURI)
Subjects: Q Science > Q Science (General)
Uncontrolled Keywords: acetylcholine (ACh); Ca2+ signalling; InsP3 receptor (IP3R); Orai;, pancreatic acinar cell (PAC); store-operated Ca2+ entry (SOCE)
Publisher: Biochemical Society
ISSN: 0264-6021
Funders: MRC
Last Modified: 04 Jun 2017 03:31

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