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2015 ; 11
(11
): 2127-2129
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gab.com Text
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GABARAP-mediated targeting of PI4K2A/PI4KII? to autophagosomes regulates
PtdIns4P-dependent autophagosome-lysosome fusion
#MMPMID26391226
Albanesi J
; Wang H
; Sun HQ
; Levine B
; Yin H
Autophagy
2015[Nov]; 11
(11
): 2127-2129
PMID26391226
show ga
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.