GABARAP recruits PI4KIIα to autophagosomes. Depletion of either GABARAP or PI4KIIα by siRNA, or overexpression of the dominant negative kinase-dead PI4KIIα, blocks autophagic flux by inhibiting autophagosome fusion with lysosomes to generate grossly enlarged autophagosomes.
These defects are rescued by either overexpressing PI4KIIα or by “shuttling” PI4P. Thus, GABARAP promotes PI4KIIα membrane trafficking to autophagosomes, and PI4P generation in situ promotes autophagosome: lysosome fusion.
Abnormally large phagosome in a PI4KIIα-depleted cell.
Autophagosomes (green) and lysosomes (red)in PI4KIIα-depleted cells during autophagy.
Autophagosomes and lysosomes in PI4KIIα-depleted cells during autophagy.