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Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease

Morgan, Anthony J., Platt, Frances M., Lloyd‑Evans, Emyr ORCID: and Galione, Antony 2011. Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease. Biochemical Journal 439 (3) , pp. 349-374. 10.1042/BJ20110949

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Endosomes, lysosomes and lysosome-related organelles are emerging as important Ca2+ storage cellular compartments with a central role in intracellular Ca2+ signalling. Endocytosis at the plasma membrane forms endosomal vesicles which mature to late endosomes and culminate in lysosomal biogenesis. During this process, acquisition of different ion channels and transporters progressively changes the endolysosomal luminal ionic environment (e.g. pH and Ca2+) to regulate enzyme activities, membrane fusion/fission and organellar ion fluxes, and defects in these can result in disease. In the present review we focus on the physiology of the inter-related transport mechanisms of Ca2+ and H+ across endolysosomal membranes. In particular, we discuss the role of the Ca2+-mobilizing messenger NAADP (nicotinic acid adenine dinucleotide phosphate) as a major regulator of Ca2+ release from endolysosomes, and the recent discovery of an endolysosomal channel family, the TPCs (two-pore channels), as its principal intracellular targets. Recent molecular studies of endolysosomal Ca2+ physiology and its regulation by NAADP-gated TPCs are providing exciting new insights into the mechanisms of Ca2+-signal initiation that control a wide range of cellular processes and play a role in disease. These developments underscore a new central role for the endolysosomal system in cellular Ca2+ regulation and signalling.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QP Physiology
R Medicine > R Medicine (General)
Uncontrolled Keywords: ATPase; calcium store; endolysosome; nicotinic acid adenine dinucleotide phosphate (NAADP); pH; two-pore channel (TPC)
Publisher: Biochemical Society
ISSN: 0264-6021
Last Modified: 19 Oct 2022 10:19

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