The lysosomal adaptor JIP3 activates dynein-dynactin via a short coiled coil

Abstract

AbstractTransport of organelles is critical for maintaining healthy neurons. A key adaptor for moving lysosomes in axons is JIP3, which binds both kinesin and dynein motors. Unlike many known dynein adaptors JIP3 contains only a short coiled coil, raising the question of whether, like them, it can activate long distance transport. Here we show a short construct of JIP3 containing residues 1-185 is sufficient to stimulate long distance movement of dynein-dynactin in vitro. Using cryoEM to solve the structure of the resulting complexes on microtubules we describe how one copy of JIP3 recruits two dyneins to dynactin. The data show that even short adaptors lacking an interaction with dynactin’s pointed end are sufficient to activate motility.