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. 2011 Feb;14(2):173-80.
doi: 10.1038/nn.2712. Epub 2010 Dec 26.

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

Christophe Altier  1 , Agustin Garcia-Caballero, Brett Simms, Haitao You, Lina Chen, Jan Walcher, H William Tedford, Tamara Hermosilla, Gerald W Zamponi
Affiliations

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

Christophe Altier et al. Nat Neurosci. 2011 Feb.

Abstract

It 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.

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