title: Mid-range Ca2+ signalling mediated by functional coupling between store-operated Ca2+ entry and IP3-dependent Ca2+ release.
abstract: The versatility and universality of Ca(2+) signals stem from the breadth of their spatial and temporal dynamics. Spatially, Ca(2+) signalling is well studied in the microdomain scale, close to a Ca(2+) channel, and at the whole-cell level. However, little is known about how local Ca(2+) signals are regulated to specifically activate spatially distant effectors without a global Ca(2+) rise. Here we show that an intricate coupling between the inositol 1,4,5 trisphosphate (IP3) receptor, SERCA pump and store-operated Ca(2+) entry (SOCE) allows for efficient mid-range Ca(2+) signalling. Ca(2+) flowing through SOCE is taken up into the ER lumen by the SERCA pump, only to be re-released by IP3Rs to activate distal Ca(2+)-activated Cl(-) channels (CaCCs). This CaCC regulation contributes to setting the membrane potential of the cell. Hence functional coupling between SOCE, SERCA and IP3R limits local Ca(2+) diffusion and funnels Ca(2+) through the ER lumen to activate a spatially separate Ca(2+) effector.
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, PO Box 24144, Doha, Qatar.
authors.forename: Raphaël
authors.initials: R
authors.lastname: Courjaret
authors.affiliation: Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Education City, Qatar Foundation, PO Box 24144, Doha, Qatar.
authors.forename: Khaled
authors.initials: K
authors.lastname: Machaca
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects; D003593:Cytoplasm / Q000187:drug effects / Q000378:metabolism; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D005260:Female; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006493:Heparin / Q000494:pharmacology; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D015640:Ion Channel Gating / Q000187:drug effects; D021962:Membrane Microdomains / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D009865:Oocytes / Q000187:drug effects / Q000378:metabolism; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000378:metabolism; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014982:Xenopus laevis
chemical_list: D015220:Calcium Channels; D053496:Inositol 1,4,5-Trisphosphate Receptors; D049452:Green Fluorescent Proteins; D004533:Egtazic Acid; D015544:Inositol 1,4,5-Trisphosphate; D006493:Heparin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium