Higher order assembly of Sorting Nexin 16 controls tubulation and distribution of neuronal endosomes

The activities of neuronal signaling receptors depend on the maturation state of the endosomal compartments in which they reside. However, it remains unclear how the distribution of these compartments within the uniquely complex morphology of neurons is regulated, and how this distribution itself affects signaling. Here we identified mechanisms by which Sorting Nexin 16 (SNX16) controls neuronal endosomal maturation and distribution. We found that higher-order assembly of SNX16 via its coiled-coil domain drives membrane tubulation in vitro and endosome association in cells. In Drosophila motor neurons, activation of Rab5 and coiled-coil-dependent self-association of SNX16 lead to its endosomal enrichment, concomitant with depletion of SNX16-positive endosomes from the synapse, and their accumulation as Rab5- and Rab7-positive tubulated compartments at the cell body. This leads to higher levels of synaptic growth-promoting BMP receptors at the cell body, and correlates with increased synaptic growth. Our results indicate that Rab regulation of SNX16 assembly controls the endosomal distribution and signaling activities of neuronal receptors.