UCL logo

UCL Discovery

UCL home » Library Services » Electronic resources » UCL Discovery

The inhibition of functional expression of calcium channels by prion protein demonstrates competition with α2δ for GPI-anchoring pathways.

Alvarez-Laviada, A; Kadurin, I; Senatore, A; Chiesa, R; Dolphin, AC; (2013) The inhibition of functional expression of calcium channels by prion protein demonstrates competition with α2δ for GPI-anchoring pathways. Biochem J , 458 (2) pp. 365-374. 10.1042/BJ20131405. Green open access

[img]
Preview
PDF
4580365.pdf

Download (701kB)

Abstract

It has recently been shown that prion protein (PrP) and the calcium channel auxiliary α2δ subunits interact in neurons and expression systems. We examined whether there was an effect of PrP on calcium currents. We show that when PrP is co-expressed with calcium channels formed from CaV2.1/β and α2δ-1 or α2δ-2, this results in a consistent decrease in calcium current density. This reduction was absent when PrP lacked its glycosyl-phosphatidylinositol (GPI) anchor. We have found that α2δ subunits are able to form GPI-anchored proteins [2] and present further evidence here. We have recently characterised a C-terminally truncated α2δ-1 construct, α2δ-1ΔC, and found that, despite loss of its membrane anchor, it still shows partial ability to increase calcium currents. We now find that PrP does not inhibit CaV2.1/β currents formed with α2δ-1ΔC rather than α2δ-1. It is possible that PrP and α2δ-1 compete for GPI-anchor intermediates or trafficking pathways, or that interaction between PrP and α2δ-1 requires association in cholesterol-rich membrane microdomains. Our additional finding that CaV2.1/β1b/α2δ-1 currents were inhibited by GPI-GFP but not by cytosolic GFP, indicates that competition for limited GPI-anchor intermediates or trafficking proteins may be involved in PrP suppression of α2δ subunit function.

Type: Article
Title: The inhibition of functional expression of calcium channels by prion protein demonstrates competition with α2δ for GPI-anchoring pathways.
Open access status: An open access version is available from UCL Discovery
DOI: 10.1042/BJ20131405
Publisher version: http://dx.doi.org/10.1042/BJ20131405
Language: English
Additional information: © 2014 The Author(s) The author(s) has paid for this article to be freely available under the terms of the Creative Commons Attribution Licence (CC-BY)(http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution and reproduction in any medium, provided the original work is properly cited.
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
URI: http://discovery.ucl.ac.uk/id/eprint/1420568
Downloads since deposit
163Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item