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

J Cell Biol. 2019 Aug 5;218(8):2600-2618. doi: 10.1083/jcb.201811074. Epub 2019 Jun 28.


The activities of neuronal signaling receptors depend heavily 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 (CC) domain drives membrane tubulation in vitro and endosome association in cells. In Drosophila melanogaster motor neurons, activation of Rab5 and CC-dependent self-association of SNX16 lead to its endosomal enrichment, accumulation in Rab5- and Rab7-positive tubulated compartments in the cell body, and concomitant depletion of SNX16-positive endosomes from the synapse. This results in accumulation of synaptic growth-promoting bone morphogenetic protein receptors in 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 receptors in neurons.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bone Morphogenetic Protein Receptors / metabolism
  • Cell Body / metabolism
  • Drosophila Proteins / chemistry
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / metabolism*
  • Endosomes / metabolism*
  • Humans
  • Models, Biological
  • Motor Neurons / metabolism*
  • Mutant Proteins / metabolism
  • Neuromuscular Junction / metabolism
  • Phosphatidylinositol Phosphates / metabolism
  • Protein Domains
  • Protein Multimerization
  • Signal Transduction
  • Sorting Nexins / chemistry
  • Sorting Nexins / metabolism*
  • rab GTP-Binding Proteins / metabolism


  • Drosophila Proteins
  • Mutant Proteins
  • Phosphatidylinositol Phosphates
  • SNX16 protein, Drosophila
  • SNX16 protein, human
  • Sorting Nexins
  • phosphatidylinositol 3-phosphate
  • Bone Morphogenetic Protein Receptors
  • rab GTP-Binding Proteins

Associated data

  • PDB/5GW0