Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
Volume 1866, Issue 7, Pages 1111-1123Publisher
ELSEVIER
DOI: 10.1016/j.bbamcr.2018.10.020
Keywords
TRPML; TRPML1; TRPML3; TPC; TPC1; TPC2
Categories
Funding
- DFG - German Research Foundation [SFB/TRR152 P04]
- NCL (Neuronal Ceroid Lipofuscinosis) Foundation Award 2016 (Hamburg, Germany)
- Mucolipidosis IV Foundation Grant [MDBR-17-120-ML4]
- Care-for-Rare Foundation Award (Munich, Germany) 2017
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Background: The endolysosomal, non-selective cation channels, two-pore channels (TPCs) and mucolipins (TRPMLs), regulate intracellular membrane dynamics and autophagy. While partially compensatory for each other, isoform-specific intracellular distribution, cell-type expression patterns, and regulatory mechanisms suggest different channel isoforms confer distinct properties to the cell. Scope of review: Briefly, established TPC/TRPML functions and interaction partners ('interactomes') are discussed. Novel TRPML3 interactors are shown, and a meta-analysis of experimentally obtained channel interactomes conducted. Accordingly, interactomes are compared and contrasted, and subsequently described in detail for TPC1, TPC2, TRPML1, and TRPML3. Major conclusions: TPC interactomes are well-defined, encompassing intracellular membrane organisation proteins. TRPML interactomes are varied, encompassing cardiac contractility- and chaperone-mediated autophagy proteins, alongside regulators of intercellular signalling. General significance: Comprising recently proposed targets to treat cancers, infections, metabolic disease and neurodegeneration, the advancement of TPC/TRPML understanding is of considerable importance. This review proposes novel directions elucidating TPC/TRPML relevance in health and disease. This article is part of a Special Issue entitled: ECS Meeting edited by Claus Heizmann, Joachim Krebs and Jacques Haiech.
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