Joachim Justin, Jefferies Harold B J, Razi Minoo, Frith David, Snijders Ambrosius P, Chakravarty Probir, Judith Delphine, Tooze Sharon A
Molecular Cell Biology of Autophagy, The Francis Crick Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Mass Spectrometry, The Francis Crick Institute, Lincoln's Inn Fields Laboratories, 44 Lincoln's Inn Fields, London WC2A 3LY, UK.
Mol Cell. 2015 Dec 17;60(6):899-913. doi: 10.1016/j.molcel.2015.11.018.
Starvation-induced autophagy requires activation of the ULK complex at the phagophore. Two Golgi proteins, WAC and GM130, regulate autophagy, however their mechanism of regulation is unknown. In search of novel interaction partners of WAC, we found that GM130 directly interacts with WAC, and this interaction is required for autophagy. WAC is bound to the Golgi by GM130. WAC and GM130 interact with the Atg8 homolog GABARAP and regulate its subcellular localization. GABARAP is on the pericentriolar matrix, and this dynamic pool contributes to autophagosome formation. Tethering of GABARAP to the Golgi by GM130 inhibits autophagy, demonstrating an unexpected role for a golgin. WAC suppresses GM130 binding to GABARAP, regulating starvation-induced centrosomal GABARAP delivery to the phagophore. GABARAP, unlipidated and lipidated, but not LC3B, GABARAPL1, and GATE-16, specifically promotes ULK kinase activation dependent on the ULK1 LIR motif, elucidating a unique non-hierarchical role for GABARAP in starvation-induced activation of autophagy.
饥饿诱导的自噬需要吞噬泡处的ULK复合物激活。两种高尔基体蛋白WAC和GM130调节自噬，但其调节机制尚不清楚。为了寻找WAC的新型相互作用伙伴，我们发现GM130直接与WAC相互作用，且这种相互作用是自噬所必需的。WAC通过GM130与高尔基体结合。WAC和GM130与Atg8同源物GABARAP相互作用并调节其亚细胞定位。GABARAP存在于中心粒周围基质中，这个动态池有助于自噬体形成。GM130将GABARAP拴系到高尔基体上会抑制自噬，这表明一种高尔基体蛋白具有意想不到的作用。WAC抑制GM130与GABARAP的结合，调节饥饿诱导的中心体GABARAP向吞噬泡的转运。未脂化和脂化的GABARAP，但不是LC3B、GABARAPL1和GATE-16，特异性促进依赖于ULK1 LIR基序的ULK激酶激活，阐明了GABARAP在饥饿诱导的自噬激活中独特的非层级作用。
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