Raghib, A;
Bertaso, F;
Davies, A;
Page, KM;
Meir, A;
Bogdanov, Y;
Dolphin, AC;
(2001)
Dominant-negative synthesis suppression of voltage-gated calcium channel Cav2.2 induced by truncated constructs.
Journal of Neuroscience
, 21
(21)
8495 - 8504.
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Abstract
Voltage-gated calcium channel �1 subunits consist of four domains (I–IV), each with six transmembrane segments. A number of truncated isoforms have been identified to occur as a result of alternative splicing or mutation. We have examined the functional consequences for expression of full-length Cav2.2 (�1B) of its coexpression with truncated constructs of Cav2.2. Domains I-II or domains III-IV, when expressed individually, together with the accessory subunits �1b and �2�-1, did not form functional channels. When they were coexpressed, lowdensity whole-cell currents and functional channels with properties similar to wild-type channels were observed. However, when domain I-II, domain III-IV, or domain I alone were coexpressed with full-length Cav2.2, they markedly suppressed its functional expression, although at the single channel level, when channels were recorded, there were no differences in their biophysical properties. Furthermore, when it was coexpressed with either domain I-II or domain I, the fluorescence of green fluorescent protein (GFP)–Cav2.2 and expression of Cav2.2 protein was almost abolished. Suppression does not involve sequestration of the Cav� subunit, because loss of GFP–Cav2.2 expression also occurred in the absence of � subunit, and the effect of domain I-II or domain I could not be mimicked by the cytoplasmic I-II loop of Cav2.2. It requires transmembrane segments, because the isolated Cav2.2 N terminus did not have any effect. Our results indicate that the mechanism of suppression of Cav2.2 by truncated constructs containing domain I involves inhibition of channel synthesis, which may represent a role of endogenously expressed truncated Cav isoforms.
| Type: | Article |
|---|---|
| Title: | Dominant-negative synthesis suppression of voltage-gated calcium channel Cav2.2 induced by truncated constructs |
| Open access status: | An open access version is available from UCL Discovery |
| Language: | English |
| Additional information: | This work is licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. The license allows you to copy, distribute, and transmit the work, as well as adapting it. However, you must attribute the work to the author (but not in any way that suggests that they endorse you or your use of the work), and cannot use the work for commercial purposes without prior permission of the author. If you alter or build upon this work, you can distribute the resulting work only under the same or similar license to this one. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/ or send a letter to Creative Commons, 444 Castro Street, Suite 900, Mountain View, California, 94041, USA. |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences |
| URI: | https://discovery.ucl.ac.uk/id/eprint/131345 |
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