期刊
AUTOPHAGY
卷 11, 期 11, 页码 2127-2129出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15548627.2015.1093718
关键词
autophagosome-lysosome fusion; GABARAP; palmitoylation; phosphatidylinositol 4-kinase II; phosphatidylinositol 4-phosphate
类别
资金
- NCI NIH HHS [R01 CA109618] Funding Source: Medline
For decades, phosphatidylinositol 4-phosphate (PtdIns4P) was considered primarily as a precursor in the synthesis of phosphatidylinositol(4,5)bisphosphate (PtdIns(4,5)P-2). More recently, specific functions for PtdIns4P itself have been identified, particularly in the regulation of intracellular membrane trafficking. PI4K2A/PI4KII (phosphatidylinositol 4-kinase type 2 ), one of the 4 enzymes that catalyze PtdIns4P production in mammalian cells, promotes vesicle formation from the trans-Golgi network (TGN) and endosomes. We recently identified a novel function for PI4K2A-derived PtdIns4P, as a facilitator of autophagosome-lysosome (A-L) fusion. We further showed that that this function requires the presence of the autophagic adaptor protein GABARAP (GABA[A] receptor-associated protein), which binds to PI4K2A and recruits it to autophagosomes. The mechanism whereby GABARAP-PI4K2A-PtdIns4P promotes A-L fusion remains to be defined. Based on other examples of phosphoinositide involvement in membrane trafficking, we speculate that it acts by recruiting elements of the membrane docking and fusion machinery.
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