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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Carrara, Guia 

Abstract

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.

Description

Keywords

Bax inhibitor-1, TMBIM, Golgi anti-apoptotic protein, calcium flux, cell adhesion and migration, ion channel, Animals, Apoptosis, Calcium, Camelus, Endoplasmic Reticulum, Golgi Apparatus, Humans, Ion Channels, Membrane Proteins, Neoplasms

Journal Title

Open Biol

Conference Name

Journal ISSN

2046-2441
2046-2441

Volume Title

7

Publisher

The Royal Society
Sponsorship
Medical Research Council (G0900224)
Wellcome Trust (090315/Z/09/Z)
Isaac Newton Trust (1407(k))
Wellcome Trust (085295/Z/08/Z)