Carrara Guia, Parsons Maddy, Saraiva Nuno, Smith Geoffrey L
Department of Pathology, University of Cambridge, Cambridge, CB2 1QP, UK.
Randall Division of Cell and Molecular Biophysics, King's College London, London SE1 1UL, UK.
Open Biol. 2017 May;7(5). doi: 10.1098/rsob.170045.
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 Ca 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 Ca 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.
高尔基体抗凋亡蛋白（GAAP），也被称为含跨膜Bax抑制因子1基序4（TMBIM4）或救生员4（Lfg4），在整个真核生物、原核生物以及一些正痘病毒的直系同源物中具有显著的氨基酸保守性，这表明其功能高度保守。GAAPs可调节来自高尔基体和内质网的钙水平及通量，赋予细胞对多种凋亡刺激的抗性，通过激活储存操纵性钙内流促进细胞黏附和迁移，对人类细胞的存活至关重要，并影响正痘病毒的毒力。GAAPs是驻留在高尔基体膜中的寡聚多跨膜蛋白，形成阳离子选择性离子通道，这或许可以解释这些蛋白的多种功能。已确定了对离子传导孔有贡献的残基，并为GAAP这些截然不同的功能之间的机制联系提供了初步线索。尽管GAAPs天然是寡聚体，但它们也可以作为单体发挥作用，这一特征将它们与其他必须寡聚化才能发挥功能的病毒编码离子通道区分开来。本综述总结了GAAPs的已知功能，并讨论了它们在疾病中的潜在重要性。
