Two-pore channels form homo- and heterodimers.
J Biol Chem
; 286(43): 37058-62, 2011 Oct 28.
Article
in En
| MEDLINE
| ID: mdl-21903581
ABSTRACT
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Calcium Channels
/
Protein Multimerization
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
J Biol Chem
Year:
2011
Document type:
Article
Affiliation country:
Reino Unido