【摘 要】
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NRBF2 (Nuclear receptor binding factor 2), a stable component of Beclin1-VPS34 complex,modulates the VPS34 kinase activity and autophagy.NRBF2 function is h
【机 构】
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Department of Neurology and Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Moun
【出 处】
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The 7th International Symposium on Autophagy 2015(第七届自噬国际研讨会
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NRBF2 (Nuclear receptor binding factor 2), a stable component of Beclin1-VPS34 complex,modulates the VPS34 kinase activity and autophagy.NRBF2 function is highly conserved through yeast (ATG38 is the yeast homolog of NRBF2) to mammalian system.Mechanistically,NRBF2/ATG38 facilitates the assembly of ATG14L-Beclin1/ATG6-VPS34 complex, thus regulating autophagosome biogenesis.Unlike ATG14L, Beclin1, or VPS34, which are essential for autophagy, NRBF2 deletion only leads to partial block of autophagy, evident by the remaining 25% of ATG14L-linked VPS34 kinase activity in NRBF2 KO cells or animals.In fact,the basal autophagy is modestly affected in NRBF2 KO cells, but stress-induced autophagy is severely impaired.We found that ER stress causes marked increase of cell death in NRBF2 KO cells, accompanied by impairment of autophagy activation.We proposed that NRBF2 KO cells or animals provide a unique model to study the roles of autophagy in human pathological conditions.Furthermore, NRBF2 KO mice display no sign of neurodegeneration, while the accumulation of autophagic substrate p62 in regional brain is apparent, suggesting altered basal autophagy in a brain area-dependent manner.Interestingly NRBF2 KO mice showed impaired memory in multiple behavioral analyses.Collectively, our study implicates NRBF2, a modulator of VPS34 activity, in regulating neuronal function and memory.
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