PDF(Pubmed)
Abstract：
The evolutionarily conserved ATG4 cysteine proteases regulate macroautophagy/autophagy through the priming and deconjugation of the Atg8-family proteins. In mammals there are four ATG4 family members (ATG4A, ATG4B, ATG4C, ATG4D) but ATG4D has been relatively understudied. Heightened interest in ATG4D has been stimulated by recent links to human disease. Notably, genetic variations in human ATG4D were implicated in a heritable neurodevelopmental disorder. Genetic analyses in dogs, along with loss-of-function zebrafish and mouse models, further support a neuroprotective role for ATG4D. Here we discuss the evidence connecting ATG4D to neurological diseases and other pathologies and summarize its roles in both autophagy-dependent and autophagy-independent cellular processes.Abbrevation: ATG: autophagy related; BafA1: bafilomycin A1; BCL2: BCL2 apoptosis regulator; BH3: BCL2 homology region 3; CASP3: caspase 3; EV: extracellular vesicle; GABA: gamma aminobutyric acid; GABARAP: GABA type A receptor-associated protein; GABARAPL1: GABA type A receptor associated protein like 1; GABARAPL2: GABA type A receptor associated protein like 2; GFP: green fluorescent protein; LIR: LC3-interacting region; MAP1LC3: microtubule associated protein 1 light chain 3; MEF: mouse embryonic fibroblast; MYC: MYC proto-oncogene, bHLH transcription factor; PE: phosphatidylethanolamine; PS: phosphatidylserine; QKO: quadruple knockout; SDS-PAGE: sodium dodecyl sulfate-polyacrylamide gel; SQSTM1: sequestosome 1.
摘要：
进化上保守的ATG4半胱氨酸蛋白酶通过Atg8家族蛋白的启动和去偶联来调节巨自噬/自噬。在哺乳动物中有四个ATG4家族成员(ATG4A,ATG4B,ATG4C,ATG4D），但ATG4D的研究相对不足。最近与人类疾病的联系激发了人们对ATG4D的浓厚兴趣。值得注意的是,人类ATG4D的遗传变异与遗传性神经发育障碍有关。狗的遗传分析，以及功能丧失的斑马鱼和小鼠模型，进一步支持ATG4D的神经保护作用。在这里，我们讨论了将ATG4D与神经系统疾病和其他病理联系起来的证据，并总结了其在自噬依赖性和自噬非依赖性细胞过程中的作用。
