InsP3 receptors and Orai channels in pancreatic acinar cells: co-localization and its consequences
Open Access
- 13 May 2011
- journal article
- research article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 436 (2), 231-239
- https://doi.org/10.1042/bj20110083
Abstract
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.Keywords
This publication has 30 references indexed in Scilit:
- Polarized but Differential Localization and Recruitment of STIM1, Orai1 and TRPC Channels in Secretory CellsTraffic, 2010
- TRPC3 Regulates Agonist-stimulated Ca2+ Mobilization by Mediating the Interaction between Type I Inositol 1,4,5-Trisphosphate Receptor, RACK1, and Orai1Published by Elsevier BV ,2010
- Ribosome-free Terminals of Rough ER Allow Formation of STIM1 Puncta and Segregation of STIM1 from IP3 ReceptorsCurrent Biology, 2009
- The elementary unit of store-operated Ca2+ entry: local activation of CRAC channels by STIM1 at ER–plasma membrane junctionsThe Journal of cell biology, 2006
- A mutation in Orai1 causes immune deficiency by abrogating CRAC channel functionNature, 2006
- STIM Is a Ca2+ Sensor Essential for Ca2+-Store-Depletion-Triggered Ca2+ InfluxCurrent Biology, 2005
- Store-Operated Calcium ChannelsPhysiological Reviews, 2005
- Polarized Expression of Ca2+ Pumps in Pancreatic and Salivary Gland CellsPublished by Elsevier BV ,1997
- Ataxia and epileptic seizures in mice lacking type 1 inositol 1,4,5-trisphosphate receptorNature, 1996
- ‘Quanta’ Ca2+ release and the control of Ca2+ entry by inositol phosphates ‐ a possible mechanismFEBS Letters, 1990