Golgi Anti-apoptotic Proteins Are Highly Conserved Ion Channels That Affect Apoptosis and Cell Migration
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Authors
Carrara, Guia
Saraiva, Nuno
Parsons, Maddy
Byrne, Bernadette
Prole, David Lawrence
Publication Date
2015-02-24Journal Title
Journal of Biological Chemistry
Volume
290
Pages
11785-11801
Language
English
Type
Article
This Version
VoR
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Carrara, G., Saraiva, N., Parsons, M., Byrne, B., Prole, D. L., Taylor, C. W., & Smith, G. L. (2015). Golgi Anti-apoptotic Proteins Are Highly Conserved Ion Channels That Affect Apoptosis and Cell Migration. Journal of Biological Chemistry, 290 11785-11801. https://doi.org/10.1074/jbc.M115.637306
Abstract
Golgi anti-apoptotic proteins (GAAPs) are multitransmembrane proteins that are expressed in the Golgi apparatus and are able to homo-oligomerize. They are highly conserved throughout eukaryotes and are present in some prokaryotes and orthopoxviruses. Within eukaryotes, GAAPs regulate the Ca(2+) content of intracellular stores, inhibit apoptosis, and promote cell adhesion and migration. Data presented here demonstrate that purified viral GAAPs (vGAAPs) and human Bax inhibitor 1 form ion channels and that vGAAP from camelpox virus is selective for cations. Mutagenesis of vGAAP, including some residues conserved in the recently solved structure of a related bacterial protein, BsYetJ, altered the conductance (E207Q and D219N) and ion selectivity (E207Q) of the channel. Mutation of residue Glu-207 or -178 reduced the effects of GAAP on cell migration and adhesion without affecting protection from apoptosis. In contrast, mutation of Asp-219 abrogated the anti-apoptotic activity of GAAP but not its effects on cell migration and adhesion. These results demonstrate that GAAPs are ion channels and define residues that contribute to the ion-conducting pore and affect apoptosis, cell adhesion, and migration independently.
Sponsorship
BBSRC (BB/L000075/1)
MRC (G0900224)
Identifiers
External DOI: https://doi.org/10.1074/jbc.M115.637306
This record's URL: https://www.repository.cam.ac.uk/handle/1810/266156