title: Ribosome-free terminals of rough ER allow formation of STIM1 puncta and segregation of STIM1 from IP(3) receptors.
abstract: Store-operated Ca(2+) entry is a ubiquitous mechanism that prevents the depletion of endoplasmic reticulum (ER) calcium. A reduction of ER calcium triggers translocation of STIM proteins, which serve as calcium sensors in the ER, to subplasmalemmal puncta where they interact with and activate Orai channels. In pancreatic acinar cells, inositol 1,4,5-trisphosphate (IP(3)) receptors populate the apical part of the ER. Here, however, we observe that STIM1 translocates exclusively to the lateral and basal regions following ER Ca(2+) loss. This finding is paradoxical because the basal and lateral regions of the acinar cells contain rough ER (RER); the size of the ribosomes that decorate RER is larger than the distance that can be spanned by a STIM-Orai complex, and STIM1 function should therefore not be possible. We resolve this paradox and characterize ribosome-free terminals of the RER that form junctions between the reticulum and the plasma membrane in the basal and lateral regions of the acinar cells. Our findings indicate that different ER compartments specialize in different calcium-handling functions (Ca(2+) release and Ca(2+) reloading) and that any potential interference between Ca(2+) release and Ca(2+) influx is minimized by the spatial separation of the two processes.
authors.affiliation: Department of Physiology, School of Biomedical Sciences, University of Liverpool, Liverpool L69 3BX, UK.
authors.forename: Gyorgy
authors.initials: G
authors.lastname: Lur
authors.forename: Lee P
authors.initials: LP
authors.lastname: Haynes
authors.forename: Ian A
authors.initials: IA
authors.lastname: Prior
authors.forename: Oleg V
authors.initials: OV
authors.lastname: Gerasimenko
authors.forename: Stefan
authors.initials: S
authors.lastname: Feske
authors.forename: Ole H
authors.initials: OH
authors.lastname: Petersen
authors.forename: Robert D
authors.initials: RD
authors.lastname: Burgoyne
authors.forename: Alexei V
authors.initials: AV
authors.lastname: Tepikin
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D018613:Microscopy, Confocal; D008854:Microscopy, Electron; D010179:Pancreas / Q000166:cytology; D010957:Plasmids / Q000235:genetics; D021381:Protein Transport / Q000502:physiology; D012270:Ribosomes / Q000378:metabolism; D000071737:Stromal Interaction Molecule 1
chemical_list: D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008562:Membrane Glycoproteins; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D002118:Calcium