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

Fingerprint

Protein Transport
GABA-A Receptors
Lysosomes
Phosphatidylinositols
Phosphatidylinositol 4,5-Diphosphate
Intracellular Membranes
Proteins
Membrane Fusion
1-Phosphatidylinositol 4-Kinase
Endosomes
Autophagosomes
phosphatidylinositol 4-phosphate
Membranes
Enzymes

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

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title = "GABARAP-mediated targeting of PI4K2A/PI4KIIatα 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/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.",
keywords = "Autophagosome-lysosome fusion, GABARAP, Palmitoylation, Phosphatidylinositol 4-kinase IIa, Phosphatidylinositol 4-phosphate",
author = "Joseph Albanesi and Hanzhi Wang and Sun, {Hui Qiao} and Beth Levine and Helen Yin",
year = "2015",
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T1 - GABARAP-mediated targeting of PI4K2A/PI4KIIatα autophagosomes regulates PtdIns4P-dependent autophagosome-lysosome fusion

AU - Albanesi, Joseph

AU - Wang, Hanzhi

AU - Sun, Hui Qiao

AU - Levine, Beth

AU - Yin, Helen

PY - 2015/1/1

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N2 - 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.

AB - 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.

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