FYCO1: linking autophagosomes to microtubule plus end-directing molecular motors

In mammalian cells, autophagosomes are transported along microtubule tracks to fuse with late endosomes or lysosomes. Autophagosomal membranes harbor the lipid phosphatidylinositol-3-phosphate (PtdIns(3)P) and phosphatidylethanolamine-conjugated ATG8/LC3/GABARAP family proteins. The small GTPase Rab7 is implicated in autophagosomal transport and fusion. We have recently reported that a previously uncharacterized protein FYVE and coiled-coil domain-containing 1 (FYCO1) functions as an adapter linking autophagosomes to microtubule plus end-directed molecular motors. FYCO1 binds to both LC3, PtdIns(3)P and Rab7, and contains a domain responsible for microtubule plus end-dependent transport. When cells are depleted for FYCO1, autophagosomes accumulate in perinuclear clusters, whereas overexpression of FYCO1 redistributes Rab7-positive vesicles to microtubule plus ends at the cell periphery. FYCO1 is likely selectively recruited to autophagosomal membranes via a mechanism involving a conformational change upon LC3-LIR interaction to expose the FYVE domain for PtdIns(3)P binding.