The Cavβ subunit prevents RFP2-mediated ubiquitination and proteasomal degradation of L-type channels

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dc.contributor.authorAltier, Christophe
dc.contributor.authorYou, Haitao
dc.contributor.authorChen, Lina
dc.contributor.authorWalcher, Jan
dc.contributor.authorHermosilla, Tamara
dc.contributor.authorGarcía-Caballero, Agustín
dc.contributor.authorSimms, Brent A.
dc.contributor.authorTedford, H. William
dc.contributor.authorZamponi, Gerald W.
dc.date.accessioned2018-05-24T13:45:15Z
dc.date.available2018-05-24T13:45:15Z
dc.date.issued2011-02
dc.description.abstractIt is well established that the auxiliary Cavβ subunit regulates calcium channel density in the plasma membrane, but the cellular mechanism by which this occurs has remained unclear. We found that the Cavβ subunit increased membrane expression of Cav1.2 channels by preventing the entry of the channels into the endoplasmic reticulum-associated protein degradation (ERAD) complex. Without Cavβ, Cav1.2 channels underwent robust ubiquitination by the RFP2 ubiquitin ligase and interacted with the ERAD complex proteins derlin-1 and p97, culminating in targeting of the channels to the proteasome for degradation. On treatment with the proteasomal inhibitor MG132, Cavβ-free channels were rescued from degradation and trafficked to the plasma membrane. The coexpression of Cavβ interfered with ubiquitination and targeting of the channel to the ERAD complex, thereby facilitating export from the endoplasmic reticulum and promoting expression on the cell surface. Thus, Cavββ regulates the ubiquitination and stability of the calcium channel complex.en_US
dc.identifier.citationAltier, C., Garcia-Caballero, A., Simms, B., You, H., Chen, L., Walcher, J., … Zamponi, G. W. (2011). The Cavβ subunit prevents RFP2-mediated ubiquitination and proteasomal degradation of L-type channels. In Nature Neuroscience (Vol. 14, pp. 173–182). https://doi.org/10.1038/nn.2712en_US
dc.identifier.doihttp://dx.doi.org/10.1038/nn.2712en_US
dc.identifier.urihttp://hdl.handle.net/1880/106656
dc.language.isoenen_US
dc.publisherNatureen_US
dc.publisher.departmentPhysiology & Pharmacologyen_US
dc.publisher.facultyCumming School of Medicineen_US
dc.publisher.institutionUniversity of Calgaryen_US
dc.rights.urihttps://creativecommons.org/licenses/by/4.0en_US
dc.titleThe Cavβ subunit prevents RFP2-mediated ubiquitination and proteasomal degradation of L-type channelsen_US
dc.typejournal articleen_US
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