FYCO1 is a Rab7 effector that binds to LC3 and PI3P to mediate microtubule plus end–directed vesicle transport

TLDR

Autophagy is the primary eukaryotic degradation pathway for long‑lived proteins, aggregates, and organelles, yet the mechanism of cytosolic transport of autophagosomes remains poorly understood. The study aims to propose a mechanism for selective recruitment of FYCO1 to autophagosomal membranes. The authors characterized FYCO1’s LC3, Rab7, and PI3P‑binding domains, mapped a CC region essential for microtubule plus‑end transport, and outlined how FYCO1 is selectively recruited to autophagosomal membranes. They identified an adaptor complex of LC3, Rab7, and FYCO1 that drives microtubule plus‑end–directed transport of autophagic vesicles.

Abstract

Autophagy is the main eukaryotic degradation pathway for long-lived proteins, protein aggregates, and cytosolic organelles. Although the protein machinery involved in the biogenesis of autophagic vesicles is well described, very little is known about the mechanism of cytosolic transport of autophagosomes. In this study, we have identified an adaptor protein complex, formed by the two autophagic membrane-associated proteins LC3 and Rab7 and the novel FYVE and coiled-coil (CC) domain–containing protein FYCO1, that promotes microtubule (MT) plus end–directed transport of autophagic vesicles. We have characterized the LC3-, Rab7-, and phosphatidylinositol-3-phosphate–binding domains in FYCO1 and mapped part of the CC region essential for MT plus end–directed transport. We also propose a mechanism for selective autophagosomal membrane recruitment of FYCO1.