GABARAP-mediated targeting of PI4K2A/PI4KIIatα autophagosomes regulates PtdIns4P-dependent autophagosome-lysosome fusion

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Abstract

For decades, phosphatidylinositol 4-phosphate (PtdIns4P) was considered primarily as a precursor in the synthesis of phosphatidylinositol(4,5) bisphosphate (PtdIns(4,5)P2). More recently, specific functions for PtdIns4P itself have been identified, particularly in the regulation of intracellular membrane trafficking. PI4K2A/PI4KIIa(phosphatidylinositol 4-kinase type 2 a), one of the 4 enzymes that catalyze PtdIns4P production in mammalian cells, promotes vesicle formation from thetransGolgi 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.

Original languageEnglish (US)
Pages (from-to)2127-2129
Number of pages3
JournalAutophagy
Volume11
Issue number11
DOIs
StatePublished - Jan 1 2015

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Keywords

  • Autophagosome-lysosome fusion
  • GABARAP
  • Palmitoylation
  • Phosphatidylinositol 4-kinase IIa
  • Phosphatidylinositol 4-phosphate

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

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