Autophagy is a spatially regulated process in axons; autophagosomes form preferentially in the distal axon tip then move actively and processively toward the cell body. Despite the primarily unidirectional transport observed in live-cell imaging experiments, both anterograde-directed KIF5/kinesin-1 motors and retrograde-directed dynein motors are tightly associated with axonal autophagosomes. Here, we discuss our recent work identifying the scaffolding protein MAPK8IP1/JIP1 (mitogen-activated protein kinase 8 interacting protein 1) as a key regulator of autophagosome transport in neurons. MAPK8IP1 tightly coordinates motor activity to ensure the fidelity of retrograde autophagosome transport in the axon.
Keywords: JIP1; LC3; LIR; MKP1; autophagosomes; axonal transport; dynactin; dynein; kinesin; motor regulation.