Full metadata record
DC Field | Value | Language |
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dc.contributor.author | Yeon, Jun Hee | - |
dc.contributor.author | Park, Cheon-Gyu | - |
dc.contributor.author | Hille, Bertil | - |
dc.contributor.author | Suh, Byung-Chang | - |
dc.date.accessioned | 2018-11-20T02:13:04Z | - |
dc.date.available | 2018-11-20T02:13:04Z | - |
dc.date.created | 2018-11-02 | - |
dc.date.issued | 2018-10 | - |
dc.identifier.citation | Proceedings of the National Academy of Sciences of the United States of America, v.115, no.42, pp.E9934 - E9943 | - |
dc.identifier.issn | 0027-8424 | - |
dc.identifier.uri | http://hdl.handle.net/20.500.11750/9423 | - |
dc.description.abstract | β subunits of high voltage-gated Ca2+ (CaV) channels promote cellsurface expression of pore-forming α1 subunits and regulate channel gating through binding to the α-interaction domain (AID) in the first intracellular loop. We addressed the stability of CaV α1B-β interactions by rapamycin-translocatable CaV β subunits that allow drug-induced sequestration and uncoupling of the β subunit from CaV2.2 channel complexes in intact cells. Without CaV α1B/α2δ1, all modified β subunits, except membrane-tethered β2a and β2e, are in the cytosol and rapidly translocate upon rapamycin addition to anchors on target organelles: Plasma membrane, mitochondria, or endoplasmic reticulum. In cells coexpressing CaV α1B/α2δ1 subunits, the translocatable β subunits colocalize at the plasma membrane with α1B and stay there after rapamycin application, indicating that interactions between α1B and bound β subunits are very stable. However, the interaction becomes dynamic when other competing β isoforms are coexpressed. Addition of rapamycin, then, switches channel gating and regulation by phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] lipid. Thus, expression of free β isoforms around the channel reveals a dynamic aspect to the α1B-β interaction. On the other hand, translocatable β subunits with AID-binding site mutations are easily dissociated from CaV α1B on the addition of rapamycin, decreasing current amplitude and PI(4,5)P2 sensitivity. Furthermore, the mutations slow CaV2.2 current inactivation and shift the voltage dependence of activation to more positive potentials. Mutated translocatable β subunits work similarly in CaV2.3 channels. In sum, the strong interaction of CaV α1B-β subunits can be overcome by other free β isoforms, permitting dynamic changes in channel properties in intact cells. © 2018 National Academy of Sciences. All Rights Reserved. | - |
dc.language | English | - |
dc.publisher | National Academy of Sciences | - |
dc.title | Translocatable voltage-gated Ca2+ channel beta subunits in alpha 1-beta complexes reveal competitive replacement yet no spontaneous dissociation | - |
dc.type | Article | - |
dc.identifier.doi | 10.1073/pnas.1809762115 | - |
dc.identifier.wosid | 000447491300020 | - |
dc.identifier.scopusid | 2-s2.0-85054952846 | - |
dc.type.local | Article(Overseas) | - |
dc.type.rims | ART | - |
dc.description.journalClass | 1 | - |
dc.citation.publicationname | Proceedings of the National Academy of Sciences of the United States of America | - |
dc.contributor.nonIdAuthor | Yeon, Jun Hee | - |
dc.contributor.nonIdAuthor | Park, Cheon-Gyu | - |
dc.contributor.nonIdAuthor | Hille, Bertil | - |
dc.identifier.citationVolume | 115 | - |
dc.identifier.citationNumber | 42 | - |
dc.identifier.citationStartPage | E9934 | - |
dc.identifier.citationEndPage | E9943 | - |
dc.identifier.citationTitle | Proceedings of the National Academy of Sciences of the United States of America | - |
dc.type.journalArticle | Article | - |
dc.description.isOpenAccess | N | - |
dc.subject.keywordAuthor | voltage-gated Ca2+ channel | - |
dc.subject.keywordAuthor | Ca-V beta subunits | - |
dc.subject.keywordAuthor | chemically inducible dimerization | - |
dc.subject.keywordAuthor | rapamycin | - |
dc.subject.keywordAuthor | PI(4,5)P-2 | - |
dc.subject.keywordPlus | SENSITIVE CALCIUM-CHANNEL | - |
dc.subject.keywordPlus | SKELETAL-MUSCLE | - |
dc.subject.keywordPlus | INTERACTION DOMAIN | - |
dc.subject.keywordPlus | ALPHA(1A) SUBUNIT | - |
dc.subject.keywordPlus | INTERACTION SITE | - |
dc.subject.keywordPlus | MEMBRANE | - |
dc.subject.keywordPlus | MODULATION | - |
dc.subject.keywordPlus | RECEPTOR | - |
dc.subject.keywordPlus | TRAFFICKING | - |
dc.subject.keywordPlus | EXPRESSION | - |
dc.contributor.affiliatedAuthor | Yeon, Jun Hee | - |
dc.contributor.affiliatedAuthor | Park, Cheon-Gyu | - |
dc.contributor.affiliatedAuthor | Hille, Bertil | - |
dc.contributor.affiliatedAuthor | Suh, Byung-Chang | - |
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