Presynaptic Spinophilin Tunes Neurexin Signalling to Control Active Zone Architecture and Function

Nat Commun. 2015 Oct 16;6:8362. doi: 10.1038/ncomms9362.

Abstract

Assembly and maturation of synapses at the Drosophila neuromuscular junction (NMJ) depend on trans-synaptic neurexin/neuroligin signalling, which is promoted by the scaffolding protein Syd-1 binding to neurexin. Here we report that the scaffold protein spinophilin binds to the C-terminal portion of neurexin and is needed to limit neurexin/neuroligin signalling by acting antagonistic to Syd-1. Loss of presynaptic spinophilin results in the formation of excess, but atypically small active zones. Neuroligin-1/neurexin-1/Syd-1 levels are increased at spinophilin mutant NMJs, and removal of single copies of the neurexin-1, Syd-1 or neuroligin-1 genes suppresses the spinophilin-active zone phenotype. Evoked transmission is strongly reduced at spinophilin terminals, owing to a severely reduced release probability at individual active zones. We conclude that presynaptic spinophilin fine-tunes neurexin/neuroligin signalling to control active zone number and functionality, thereby optimizing them for action potential-induced exocytosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecules, Neuronal / metabolism*
  • Drosophila
  • Drosophila Proteins / metabolism*
  • Female
  • GTPase-Activating Proteins / metabolism
  • Male
  • Microfilament Proteins / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • PDZ Domains
  • Synapses / metabolism*
  • Synapses / ultrastructure

Substances

  • Cell Adhesion Molecules, Neuronal
  • Drosophila Proteins
  • GTPase-Activating Proteins
  • Microfilament Proteins
  • Nerve Tissue Proteins
  • Nrx protein, Drosophila
  • RhoGAP100F protein, Drosophila
  • neurabin
  • neuroligin 1

Associated data

  • PDB/4XHV