title: Bidirectional Ca²⁺ signaling occurs between the endoplasmic reticulum and acidic organelles.
abstract: The endoplasmic reticulum (ER) and acidic organelles (endo-lysosomes) act as separate Ca(2+) stores that release Ca(2+) in response to the second messengers IP3 and cADPR (ER) or NAADP (acidic organelles). Typically, trigger Ca(2+) released from acidic organelles by NAADP subsequently recruits IP3 or ryanodine receptors on the ER, an anterograde signal important for amplification and Ca(2+) oscillations/waves. We therefore investigated whether the ER can signal back to acidic organelles, using organelle pH as a reporter of NAADP action. We show that Ca(2+) released from the ER can activate the NAADP pathway in two ways: first, by stimulating Ca(2+)-dependent NAADP synthesis; second, by activating NAADP-regulated channels. Moreover, the differential effects of EGTA and BAPTA (slow and fast Ca(2+) chelators, respectively) suggest that the acidic organelles are preferentially activated by local microdomains of high Ca(2+) at junctions between the ER and acidic organelles. Bidirectional organelle communication may have wider implications for endo-lysosomal function as well as the generation of Ca(2+) oscillations and waves.
authors.affiliation: Department of Pharmacology, University of Oxford, Oxford OX1 3QT, England, UK. antony.galione@pharm.ox.ac.uk
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Morgan
authors.forename: Lianne C
authors.initials: LC
authors.lastname: Davis
authors.forename: Siegfried K T Y
authors.initials: SK
authors.lastname: Wagner
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Lewis
authors.forename: John
authors.initials: J
authors.lastname: Parrington
authors.forename: Grant C
authors.initials: GC
authors.lastname: Churchill
authors.forename: Antony
authors.initials: A
authors.lastname: Galione
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism*; D047331:Lytechinus / Q000166:cytology / Q000378:metabolism*; D009249:NADP / Q000031:analogs & derivatives / Q000096:biosynthesis
chemical_list: D002614:Chelating Agents; D004533:Egtazic Acid; D009249:NADP; C024376:NAADP; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium