Two-pore channels form homo- and heterodimers.
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...
| Main Authors: | , , , , , |
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| Format: | Journal article |
| Language: | English |
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2011
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| _version_ | 1826282863314599936 |
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| author | Rietdorf, K Funnell, T Ruas, M Heinemann, J Parrington, J Galione, A |
| author_facet | Rietdorf, K Funnell, T Ruas, M Heinemann, J Parrington, J Galione, A |
| author_sort | Rietdorf, K |
| collection | OXFORD |
| description | 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. |
| first_indexed | 2024-03-07T00:50:15Z |
| format | Journal article |
| id | oxford-uuid:8624bc40-4219-49f0-a550-1f152c980f87 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:50:15Z |
| publishDate | 2011 |
| record_format | dspace |
| spelling | oxford-uuid:8624bc40-4219-49f0-a550-1f152c980f872022-03-26T22:02:05ZTwo-pore channels form homo- and heterodimers.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8624bc40-4219-49f0-a550-1f152c980f87EnglishSymplectic Elements at Oxford2011Rietdorf, KFunnell, TRuas, MHeinemann, JParrington, JGalione, ATwo-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. |
| spellingShingle | Rietdorf, K Funnell, T Ruas, M Heinemann, J Parrington, J Galione, A Two-pore channels form homo- and heterodimers. |
| title | Two-pore channels form homo- and heterodimers. |
| title_full | Two-pore channels form homo- and heterodimers. |
| title_fullStr | Two-pore channels form homo- and heterodimers. |
| title_full_unstemmed | Two-pore channels form homo- and heterodimers. |
| title_short | Two-pore channels form homo- and heterodimers. |
| title_sort | two pore channels form homo and heterodimers |
| work_keys_str_mv | AT rietdorfk twoporechannelsformhomoandheterodimers AT funnellt twoporechannelsformhomoandheterodimers AT ruasm twoporechannelsformhomoandheterodimers AT heinemannj twoporechannelsformhomoandheterodimers AT parringtonj twoporechannelsformhomoandheterodimers AT galionea twoporechannelsformhomoandheterodimers |