Fig. 10

Proposed model of AP-4-dependent trafficking. (1) AP-4 and its accessory proteins, TEPSIN, RUSC1 and RUSC2, are recruited to the TGN membrane where they concentrate their transmembrane cargo proteins, ATG9A, SERINC1 and SERINC3, into a vesicle bud; (2) A vesicle carrying ATG9A and SERINCs, coated by AP-4 and its accessory proteins, buds from the TGN membrane; (3) AP-4 and TEPSIN fall off the vesicle membrane and are available for further rounds of vesicle budding at the TGN, while RUSCs remain associated with the vesicle; (4) The vesicle associates with microtubule transport machinery, via the RUSCs, for plus-end-directed transport to the cell periphery; (5) The peripheral ATG9A-containing vesicles act in the nucleation of autophagosomes. In neurons, microtubules are polarised with their plus-ends at the distal axon, which is an important site of autophagosome biogenesis. Thus, in AP-4-deficient neurons ATG9A may not be delivered efficiently to the distal axon, thereby disrupting the spatial control of autophagy