title: POST, partner of stromal interaction molecule 1 (STIM1), targets STIM1 to multiple transporters.
abstract: Specialized proteins in the plasma membrane, endoplasmic reticulum (ER), and mitochondria tightly regulate intracellular calcium. A unique mechanism called store-operated calcium entry is activated when ER calcium is depleted, serving to restore intra-ER calcium levels. An ER calcium sensor, stromal interaction molecule 1 (STIM1), translocates within the ER membrane upon store depletion to the juxtaplasma membrane domain, where it interacts with intracellular domains of a highly calcium-selective plasma membrane ion channel, Orai1. STIM1 gates Orai1, allowing calcium to enter the cytoplasm, where it repletes the ER store via calcium-ATPases pumps. Here, we performed affinity purification of Orai1 from Jurkat cells to identify partner of STIM1 (POST), a 10-transmembrane-spanning segment protein of unknown function. The protein is located in the plasma membrane and ER. POST-Orai1 binding is store depletion-independent. On store depletion, the protein binds STIM1 and moves within the ER to localize near the cell membrane. This protein, TMEM20 (POST), does not affect store-operated calcium entry but does reduce plasma membrane Ca(2+) pump activity. Store depletion promotes STIM1-POST complex binding to smooth ER and plasma membrane Ca(2+) ATPases (SERCAs and PMCAs, respectively), Na/K-ATPase, as well as to the nuclear transporters, importins-β and exportins.
authors.affiliation: Department of Cardiology, The Howard Hughes Medical Institute, Manton Center for Orphan Disease, Children's Hospital Boston, Boston, MA 02115, USA.
authors.forename: Grigory
authors.initials: G
authors.lastname: Krapivinsky
authors.forename: Luba
authors.initials: L
authors.lastname: Krapivinsky
authors.forename: Stephanie C
authors.initials: SC
authors.lastname: Stotz
authors.forename: Yunona
authors.initials: Y
authors.lastname: Manasian
authors.forename: David E
authors.initials: DE
authors.lastname: Clapham
mesh_terms: D001692:Biological Transport / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D004594:Electrophysiology; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008856:Microscopy, Fluorescence; D009363:Neoplasm Proteins / Q000378:metabolism*; D000071740:ORAI1 Protein; D000070590:Solute Carrier Proteins; D000071737:Stromal Interaction Molecule 1
chemical_list: D015220:Calcium Channels; D002352:Carrier Proteins; D008565:Membrane Proteins; D009363:Neoplasm Proteins; D000071740:ORAI1 Protein; C510746:ORAI1 protein, human; C569397:SLC35G1 protein, human; C103530:STIM1 protein, human; D000070590:Solute Carrier Proteins; D000071737:Stromal Interaction Molecule 1; D002118:Calcium
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