Modeling of axonal endoplasmic reticulum network by spastic paraplegia proteins

Elife. 2017 Jul 25:6:e23882. doi: 10.7554/eLife.23882.

Abstract

Axons contain a smooth tubular endoplasmic reticulum (ER) network that is thought to be continuous with ER throughout the neuron; the mechanisms that form this axonal network are unknown. Mutations affecting reticulon or REEP proteins, with intramembrane hairpin domains that model ER membranes, cause an axon degenerative disease, hereditary spastic paraplegia (HSP). We show that Drosophila axons have a dynamic axonal ER network, which these proteins help to model. Loss of HSP hairpin proteins causes ER sheet expansion, partial loss of ER from distal motor axons, and occasional discontinuities in axonal ER. Ultrastructural analysis reveals an extensive ER network in axons, which shows larger and fewer tubules in larvae that lack reticulon and REEP proteins, consistent with loss of membrane curvature. Therefore HSP hairpin-containing proteins are required for shaping and continuity of axonal ER, thus suggesting roles for ER modeling in axon maintenance and function.

Keywords: D. melanogaster; axon; axon degeneration; cell biology; endoplasmic reticulum; hereditary spastic paraplegia; neuroscience; smooth endoplasmic reticulum; ultrastructure.

MeSH terms

  • Animals
  • Axonal Transport
  • Axons / metabolism*
  • Axons / ultrastructure
  • Disease Models, Animal
  • Drosophila Proteins / deficiency
  • Drosophila Proteins / genetics*
  • Drosophila melanogaster / classification
  • Drosophila melanogaster / cytology
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / ultrastructure
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum / ultrastructure
  • Gene Expression
  • Humans
  • Larva / cytology
  • Larva / genetics
  • Larva / metabolism
  • Larva / ultrastructure
  • Membrane Transport Proteins / deficiency
  • Membrane Transport Proteins / genetics*
  • Mutation
  • Phylogeny
  • Protein Isoforms / deficiency
  • Protein Isoforms / genetics
  • Spastic Paraplegia, Hereditary / genetics*
  • Spastic Paraplegia, Hereditary / metabolism
  • Spastic Paraplegia, Hereditary / pathology

Substances

  • Drosophila Proteins
  • Membrane Transport Proteins
  • Protein Isoforms
  • REEP1 protein, human
  • ReepA protein, Drosophila
  • Rtnl1 protein, Drosophila