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Dominant-negative synthesis suppression of voltage-gated calcium channel Cav2.2 induced by truncated constructs

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. Green open access

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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 > Provost and Vice Provost Offices
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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Wolfson Inst for Biomedical Research
URI: https://discovery.ucl.ac.uk/id/eprint/131345
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