Golgi anti-apoptotic protein: a tale of camels, calcium, channels and cancer

Golgi anti-apoptotic protein (GAAP), also known as transmembrane Bax inhibitor-1 motif-containing 4 (TMBIM4) or Lifeguard 4 (Lfg4), shares remarkable amino acid conservation with orthologues throughout eukaryotes, prokaryotes and some orthopoxviruses, suggesting a highly conserved function. GAAPs re...

Full description

Saved in:
Bibliographic Details
Published in:Open biology 2017-05, Vol.7 (5), p.170045
Main Authors: Carrara, Guia, Parsons, Maddy, Saraiva, Nuno, Smith, Geoffrey L.
Format: Article
Language:English
Subjects:
Animals
Apoptosis
Bax Inhibitor-1, Tmbim
Calcium - metabolism
Calcium Flux
Camelus
Cell Adhesion And Migration
Endoplasmic Reticulum - metabolism
Golgi Anti-Apoptotic Protein
Golgi Apparatus - metabolism
Humans
Invited Review
Ion Channel
Ion Channels - metabolism
Membrane Proteins - chemistry
Membrane Proteins - genetics
Membrane Proteins - metabolism
Neoplasms - metabolism
Neoplasms - pathology
Review
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Golgi anti-apoptotic protein (GAAP), also known as transmembrane Bax inhibitor-1 motif-containing 4 (TMBIM4) or Lifeguard 4 (Lfg4), shares remarkable amino acid conservation with orthologues throughout eukaryotes, prokaryotes and some orthopoxviruses, suggesting a highly conserved function. GAAPs regulate Ca2+ levels and fluxes from the Golgi and endoplasmic reticulum, confer resistance to a broad range of apoptotic stimuli, promote cell adhesion and migration via the activation of store-operated Ca2+ entry, are essential for the viability of human cells, and affect orthopoxvirus virulence. GAAPs are oligomeric, multi-transmembrane proteins that are resident in Golgi membranes and form cation-selective ion channels that may explain the multiple functions of these proteins. Residues contributing to the ion-conducting pore have been defined and provide the first clues about the mechanistic link between these very different functions of GAAP. Although GAAPs are naturally oligomeric, they can also function as monomers, a feature that distinguishes them from other virus-encoded ion channels that must oligomerize for function. This review summarizes the known functions of GAAPs and discusses their potential importance in disease.
ISSN:2046-2441
2046-2441
DOI:10.1098/rsob.170045