Golgi Anti-Apoptotic Proteins are Highly Conserved Ion Channels that Affect Apoptosis and Cell Migration [Microbiology]

February 24th, 2015 by Carrara, G., Saraiva, N., Parsons, M., Byrne, B., Prole, D. L., Taylor, C. W., Smith, G. L.

Golgi anti-apoptotic proteins (GAAPs) are multi-transmembrane proteins that are expressed in the Golgi apparatus and are able to homo-oligomerise. They are highly conserved throughout eukaryotes and are present in some prokaryotes and orthopoxviruses. Within eukaryotes, GAAPs regulate the Ca2+ content of intracellular stores, inhibit apoptosis and promote cell adhesion and migration. Data presented here demonstrate that purified viral GAAPs (vGAAP) and human Bax inhibitor 1 (hBI-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 residues E207 or E178 reduced the effects of GAAP on cell migration and adhesion, without affecting protection from apoptosis. In contrast, mutation of D219 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.