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Do voltage-gated calcium channel alpha2delta subunits require proteolytic processing into alpha2 and delta to be functional?

L Douglas·A Davies·J Wratten·A C Dolphin
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Abstract

The accessory alpha2delta subunits of voltage-gated calcium channels are type 1 transmembrane proteins that are highly glycosylated and possess multiple disulfide bonds. From studies of the topology and processing of skeletal-muscle alpha2delta-1, it has been shown to be post-translationally cleaved into an alpha2 and a delta subunit, which remain disulfide-bonded. In the present study, we have examined the processing of alpha2delta-2 subunits when stably or transiently expressed, in tsA (temperature-sensitive A)-201, Cos-7 and NG108-15 cells, and compared it with that observed in the cerebellum. Despite showing full functionality and being expressed on the plasma membrane, the vast majority of heterologously expressed alpha2delta-2 is not cleaved into alpha(2)-2 and delta-2, unlike endogenous alpha2delta-2 in the cerebellum. It remains an open question for future research whether alpha2delta-2 is functional in its calcium channel trafficking role in its proteolytically cleaved or non-cleaved state.

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AnimalsCOS CellsCalcium ChannelsCell LineCell MembraneChlorocebus aethiopsDNA, ComplementaryGlycosylationMiceProtein Processing, Post-TranslationalProtein SubunitsRecombinant ProteinsTransfectionJournal ArticleResearch Support, Non-U.S. Gov't

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L Douglas, A Davies, J Wratten, A C Dolphin. 2006. Do voltage-gated calcium channel alpha2delta subunits require proteolytic processing into alpha2 and delta to be functional?. https://doi.org/10.1042/bst0340894

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