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

TY - JOUR

T1 - Golgi anti-apoptotic protein

T2 - A tale of camels, calcium, channels and cancer

AU - Carrara, Guia

AU - Parsons, Maddy

AU - Saraiva, Nuno

AU - Smith, Geoffrey L.

PY - 2017/5/3

Y1 - 2017/5/3

N2 - 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 ionconducting 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.

AB - 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 ionconducting 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.

KW - Bax inhibitor-1

KW - Calcium flux

KW - Cell adhesion and migration

KW - Golgi anti-apoptotic protein

KW - Ion channel

KW - TMBIM

UR - http://www.scopus.com/inward/record.url?scp=85020011420&partnerID=8YFLogxK

U2 - 10.1098/rsob.170045

DO - 10.1098/rsob.170045

M3 - Article

AN - SCOPUS:85020011420

SN - 2046-2441

VL - 7

JO - Open Biology

JF - Open Biology

IS - 5

M1 - 170045

ER -