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Two-pore channels form homo- and heterodimers

Rietdorf, Katja; Funnell, Tim M.; Ruas, Margarida; Heinemann, Jennifer; Parrington, John and Galione, Antony (2011). Two-pore channels form homo- and heterodimers. The Journal of Biological Chemistry, 286(43) pp. 37058–37062.

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Two-pore channels (TPCs) have been recently identified as NAADP-regulated Ca(2+) release channels, which are localized on the endolysosomal system. TPCs have a 12-transmembrane domain (TMD) structure and are evolutionary intermediates between the 24-TMD α-subunits of Na(+) or Ca(2+) channels and the transient receptor potential channel superfamily, which have six TMDs in a single subunit and form tetramers with 24 TMDs as active channels. Based on this relationship, it is predicted that TPCs dimerize to form functional channels, but the dimerization of human TPCs has so far not been studied. Using co-immunoprecipitation studies and a mass spectroscopic analysis of the immunocomplex, we show the presence of homo- and heteromeric complexes for human TPC1 and TPC2. Despite their largely distinct localization, we identified a discrete number of endosomes that coexpressed TPC1 and TPC2. Homo- and heteromerization were confirmed by a FRET study, showing that both proteins interacted in a rotational (N- to C-terminal/head-to-tail) symmetry. This is the first report describing the presence of homomultimeric TPC1 channels and the first study showing that TPCs are capable of forming heteromers.

Item Type: Journal Item
Copyright Holders: 2011 The American Society for Biochemistry and Molecular Biology, Inc.
ISSN: 1083-351X
Project Funding Details:
Funded Project NameProject IDFunding Body
Not SetNot SetWellcome Trust
Keywords: Calcium Channels; Calcium Signalling; Lysosomes; NAADP; Receptors; Receptor heterodimerization; Two-Pore Channel
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Related URLs:
Item ID: 38452
Depositing User: Katja Rietdorf
Date Deposited: 19 Sep 2013 10:03
Last Modified: 09 Dec 2018 03:42
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