title: A novel Ca²⁺-mediated cross-talk between endoplasmic reticulum and acidic organelles: implications for NAADP-dependent Ca²⁺ signalling.
abstract: Nicotinic acid adenine dinucleotide phosphate (NAADP) serves as the ideal trigger of spatio-temporally complex intracellular Ca(2+) signals. However, the identity of the intracellular Ca(2+) store(s) recruited by NAADP, which may include either the endolysosomal (EL) or the endoplasmic reticulum (ER) Ca(2+) pools, is still elusive. Here, we show that the Ca(2+) response to NAADP was suppressed by interfering with either EL or ER Ca(2+) sequestration. The measurement of EL and ER Ca(2+) levels by using selectively targeted aequorin unveiled that the preventing ER Ca(2+) storage also affected ER Ca(2+) loading and vice versa. This indicates that a functional Ca(2+)-mediated cross-talk exists at the EL-ER interface and exerts profound implications for the study of NAADP-induced Ca(2+) signals. Extreme caution is warranted when dissecting NAADP targets by pharmacologically inhibiting EL and/or the ER Ca(2+) pools. Moreover, Ca(2+) transfer between these compartments might be essential to regulate vital Ca(2+)-dependent processes in both organelles.
authors: Department of Pharmaceutical Sciences, Università del Piemonte Orientale "Amedeo Avogadro", 28100 Novara, Italy.
authors: Virginia
authors: V
authors: Ronco
authors: Laboratory of General Physiology, Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, 27100 Pavia, Italy.
authors: Duilio Michele
authors: DM
authors: Potenza
authors: Laboratory of General Physiology, Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, 27100 Pavia, Italy.
authors: Federico
authors: F
authors: Denti
authors: Laboratory of General Physiology, Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, 27100 Pavia, Italy.
authors: Sabrina
authors: S
authors: Vullo
authors: Laboratory of General Physiology, Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, 27100 Pavia, Italy.
authors: Giuseppe
authors: G
authors: Gagliano
authors: Laboratory of Neurophysiology, Department of Brain and Behavioural Sciences, University of Pavia, 27100 Pavia, Italy.
authors: Marialuisa
authors: M
authors: Tognolina
authors: Department of Medicine and Health Sciences, University of Molise, 86100 Campobasso, Italy.
authors: Germano
authors: G
authors: Guerra
authors: Department of Morphology, Surgery and Experimental Medicine, Section of Pathology, Oncology and Experimental Biology, Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 44121 Ferrara, ItalyfCentro Fermi, 00184 Roma, Italy.
authors: Paolo
authors: P
authors: Pinton
authors: Department of Pharmaceutical Sciences, Università del Piemonte Orientale "Amedeo Avogadro", 28100 Novara, Italy.
authors: Armando A
authors: AA
authors: Genazzani
authors: Laboratory of Neurophysiology, Department of Brain and Behavioural Sciences, University of Pavia, 27100 Pavia, Italy; Centro Fermi, 00184 Roma, Italy.
authors: Lisa
authors: L
authors: Mapelli
authors: Department of Pharmaceutical Sciences, Università del Piemonte Orientale "Amedeo Avogadro", 28100 Novara, Italy. Electronic address: dmitry.lim@pharm.unipmn.it.
authors: Dmitry
authors: D
authors: Lim
authors: Laboratory of General Physiology, Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, 27100 Pavia, Italy. Electronic address: francesco.moccia@unipv.it.
authors: Francesco
authors: F
authors: Moccia
mesh_terms: D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects*; D004151:Dipeptides / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism*; D018942:Macrolides / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D009249:NADP / Q000031:analogs & derivatives* / Q000494:pharmacology; D009550:Nigericin / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D050053:TRPM Cation Channels / Q000378:metabolism; D019284:Thapsigargin / Q000494:pharmacology
chemical_list: D004151:Dipeptides; D018942:Macrolides; D050053:TRPM Cation Channels; C437888:TRPM4 protein, human; C041865:glycylphenylalanine 2-naphthylamide; D009249:NADP; C024376:NAADP; D019284:Thapsigargin; C040929:bafilomycin A1; D009550:Nigericin; D002118:Calcium
keywords: ER calcium; Lysosomal calcium; Lysosome-ER crosstalk; NAADP; NAADP-dependent Ca(2+) signalling