Golgi anti-apoptotic proteins are highly conserved ion channels that affect apoptosis and cell migration.
Journal of Biological Chemistry
American Society for Biochemistry and Molecular Biology Inc.
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Carrara, G., Saraiva, N., Parsons, M., Byrne, B., Prole, D., Taylor, C., & Smith, G. (2015). Golgi anti-apoptotic proteins are highly conserved ion channels that affect apoptosis and cell migration.. Journal of Biological Chemistry, 290 (18), 11785-11801. https://doi.org/10.1074/jbc.M115.637306
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.
Electrophysiology, Ion Channel, Lipid Bilayer, Membrane Protein, Viral Protein, Amino Acid Sequence, Animals, Apoptosis, Cell Line, Cell Movement, Conserved Sequence, Humans, Ion Channels, Models, Molecular, Molecular Sequence Data, Mutation, Porosity, Protein Conformation
This work was supported by the United Kingdom Medical Research Council, the Biotechnology and Biological Sciences Research Council, and the Wellcome Trust
Wellcome Trust (101844/Z/13/Z)
External DOI: https://doi.org/10.1074/jbc.M115.637306
This record's URL: https://www.repository.cam.ac.uk/handle/1810/247867
Attribution 2.0 UK: England & Wales
Licence URL: http://creativecommons.org/licenses/by/2.0/uk/
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