| First Author | Alvarez-Laviada A | Year | 2014 |
| Journal | Biochem J | Volume | 458 |
| Issue | 2 | Pages | 365-74 |
| PubMed ID | 24329154 | Mgi Jnum | J:210494 |
| Mgi Id | MGI:5571254 | Doi | 10.1042/BJ20131405 |
| Citation | Alvarez-Laviada A, et al. (2014) The inhibition of functional expression of calcium channels by prion protein demonstrates competition with alpha2delta for GPI-anchoring pathways. Biochem J 458(2):365-74 |
| abstractText | It has been shown recently that PrP (prion protein) and the calcium channel auxiliary alpha2delta subunits interact in neurons and expression systems [Senatore, Colleoni, Verderio, Restelli, Morini, Condliffe, Bertani, Mantovani, Canovi, Micotti, Forloni, Dolphin, Matteoli, Gobbi and Chiesa (2012) Neuron 74, 300-313]. In the present study we examined whether there was an effect of PrP on calcium currents. We have shown that when PrP is co-expressed with calcium channels formed from CaV2.1/beta and alpha2delta-1 or alpha2delta-2, there is a consistent decrease in calcium current density. This reduction was absent when a PrP construct was used lacking its GPI (glycosylphosphatidylinositol) anchor. We have reported previously that alpha2delta subunits are able to form GPI-anchored proteins [Davies, Kadurin, Alvarez-Laviada, Douglas, Nieto-Rostro, Bauer, Pratt and Dolphin (2010) Proc. Natl. Acad. Sci. U.S.A. 107, 1654-1659] and show further evidence in the present paper. We have characterized recently a C-terminally truncated alpha2delta-1 construct, alpha2delta-1DeltaC, and found that, despite loss of its membrane anchor, it still shows a partial ability to increase calcium currents [Kadurin, Alvarez-Laviada, Ng, Walker-Gray, D'Arco, Fadel, Pratt and Dolphin (2012) J. Biol. Chem. 1287, 33554-33566]. We now find that PrP does not inhibit CaV2.1/beta currents formed with alpha2delta-1DeltaC, rather than alpha2delta-1. It is possible that PrP and alpha2delta-1 compete for GPI-anchor intermediates or trafficking pathways, or that interaction between PrP and alpha2delta-1 requires association in cholesterol-rich membrane microdomains. Our additional finding that CaV2.1/beta1b/alpha2delta-1 currents were inhibited by GPI-GFP, but not cytosolic GFP, indicates that competition for limited GPI-anchor intermediates or trafficking pathways may be involved in PrP suppression of alpha2delta subunit function. |
