A novel Ca²⁺-mediated cross-talk between endoplasmic reticulum and acidic organelles: implications for NAADP-dependent Ca²⁺ signalling.

Virginia Ronco, Duilio Michele Potenza, Federico Denti, Sabrina Vullo, Giuseppe Gagliano, Marialuisa Tognolina, Germano Guerra, Paolo Pinton, Armando A Genazzani, Lisa Mapelli, Dmitry Lim, Francesco Moccia

Journal: Cell calcium 2015;57(2):89-100

PMID: 25655285

Full Text on Elsevier Science View on PubMed

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.

Address: Department of Pharmaceutical Sciences, Università del Piemonte Orientale "Amedeo Avogadro", 28100 Novara, Italy.; Laboratory of General Physiology, Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, 27100 Pavia, Italy.; Laboratory of Neurophysiology, Department of Brain and Behavioural Sciences, University of Pavia, 27100 Pavia, Italy.; Department of Medicine and Health Sciences, University of Molise, 86100 Campobasso, Italy.; 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.; Laboratory of Neurophysiology, Department of Brain and Behavioural Sciences, University of Pavia, 27100 Pavia, Italy; Centro Fermi, 00184 Roma, Italy.; Department of Pharmaceutical Sciences, Università del Piemonte Orientale "Amedeo Avogadro", 28100 Novara, Italy. Electronic address: [email protected].; Laboratory of General Physiology, Department of Biology and Biotechnology "Lazzaro Spallanzani", University of Pavia, 27100 Pavia, Italy. Electronic address: [email protected].

DOI: 10.1016/j.ceca.2015.01.001

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MeSH Terms: Calcium, Calcium Signaling, Dipeptides, Endoplasmic Reticulum, Endosomes, HeLa Cells, Humans, Lysosomes, Macrolides, Membrane Potentials, NADP, Nigericin, Patch-Clamp Techniques, TRPM Cation Channels, Thapsigargin