title: GABARAP-mediated targeting of PI4K2A/PI4KIIα to autophagosomes regulates PtdIns4P-dependent autophagosome-lysosome fusion.
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/PI4KIIα (phosphatidylinositol 4-kinase type 2 α), 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.
authors.affiliation: a Department of Pharmacology ; University of Texas Southwestern Medical Center ; Dallas , TX USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Albanesi
authors.affiliation: b Department of Biochemistry ; University of Texas Southwestern Medical Center ; Dallas , TX USA.
authors.forename: Hanzhi
authors.initials: H
authors.lastname: Wang
authors.affiliation: c Department of Physiology ; University of Texas Southwestern Medical Center ; Dallas , TX USA.
authors.forename: Hui-Qiao
authors.initials: HQ
authors.lastname: Sun
authors.affiliation: d Department of Internal Medicine ; University of Texas Southwestern Medical Center ; Dallas , TX USA.|e Center for Autophagy Research; University of Texas Southwestern Medical Center; Dallas, TX USA.|f Howard Hughes Medical Institute; University of Texas Southwestern Medical Center ; Dallas , TX USA.
authors.forename: Beth
authors.initials: B
authors.lastname: Levine
authors.affiliation: c Department of Physiology ; University of Texas Southwestern Medical Center ; Dallas , TX USA.
authors.forename: Helen
authors.initials: H
authors.lastname: Yin
keywords: GABARAP; autophagosome-lysosome fusion; palmitoylation; phosphatidylinositol 4-kinase IIα; phosphatidylinositol 4-phosphate