Do voltage-gated calcium channel alpha2delta subunits require proteolytic processing into alpha2 and delta to be functional?
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.
Douglas
L
L
Department of Pharmacology, University College London, London WC1E 6BT, UK.
Davies
A
A
Wratten
J
J
Dolphin
A C
AC
D000818:Animals; D019556:COS Cells; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane; D002522:Chlorocebus aethiops; D018076:DNA, Complementary / Q000235:genetics; D006031:Glycosylation; D051379:Mice; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D014162:Transfection
C512066:CACNA2D1 protein, mouse; D015220:Calcium Channels; D018076:DNA, Complementary; D021122:Protein Subunits; D011994:Recombinant Proteins