IP3 receptors and Orai channels in pancreatic acinar cells: co-localisation and its consequences

György Lur , Mark W Sherwood , Etsuko Ebisui , Lee P Haynes , Stefan Feske , Robert Sutton , Robert Burgoyne , Katsuhiko Mikoshiba , Ole H Petersen , Alexei V Tepikin (1)

1 The Physiological Laboratory

Orai1 proteins have been recently identified as subunits of store-operated Ca2+ entry (SOCE) channels. In primary isolated pancreatic acinar cells, Orai1 showed remarkable co-localisation and co-immunoprecipitation with all 3 subtypes of IP3 receptors. The co-localization between Orai1 and IP3Rs was restricted to the apical part of pancreatic acinar cells. Neither co-localization nor co-immunoprecipitation was affected by the Ca2+ store depletion. Importantly we also characterised Orai1 in basal and lateral membranes of pancreatic acinar cells. The basal and lateral membranes of pancreatic acinar cells have been previously shown to accumulate STIM1 puncta as a result of store depletion. We therefore conclude that these polarized secretory cells contain two pools of Orai1 - apical that interact with IP3Rs and baso-lateral that interact with STIM1 following the Ca2+ store depletion. Experiments on IP3Rs 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 IP3-releasing secretagogue acetylcholine (ACh) produced a negative modulatory effect on SOCE, suggesting that activated IP3Rs could have an inhibitory effect on this Ca2+ entry mechanism.

Mots clés: Life Sciences

György Lur, Mark W Sherwood, Etsuko Ebisui, Lee P Haynes, Stefan Feske, et al.. IP3 receptors and Orai channels in pancreatic acinar cells: co-localisation and its consequences. Biochemical Journal, 2011, 436 (2), pp.231-239. ⟨10.1042/BJ20110083⟩. ⟨hal-00592568⟩