Neurexin-Neuroligin 1 regulates synaptic morphology and functions via the WAVE regulatory complex in Drosophila neuromuscular junction

Elife. 2018 Mar 14:7:e30457. doi: 10.7554/eLife.30457.

Abstract

Neuroligins are postsynaptic adhesion molecules that are essential for postsynaptic specialization and synaptic function. But the underlying molecular mechanisms of neuroligin functions remain unclear. We found that Drosophila Neuroligin 1 (DNlg1) regulates synaptic structure and function through WAVE regulatory complex (WRC)-mediated postsynaptic actin reorganization. The disruption of DNlg1, DNlg2, or their presynaptic partner neurexin (DNrx) led to a dramatic decrease in the amount of F-actin. Further study showed that DNlg1, but not DNlg2 or DNlg3, directly interacts with the WRC via its C-terminal interacting receptor sequence. That interaction is required to recruit WRC to the postsynaptic membrane to promote F-actin assembly. Furthermore, the interaction between DNlg1 and the WRC is essential for DNlg1 to rescue the morphological and electrophysiological defects in dnlg1 mutants. Our results reveal a novel mechanism by which the DNrx-DNlg1 trans-synaptic interaction coordinates structural and functional properties at the neuromuscular junction.

Keywords: D. melanogaster; F-actin; Neuroligin; WAVE regulatory complex; cell biology; neuroscience; postsynaptic assembly; synapse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actins / chemistry
  • Actins / genetics*
  • Animals
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules, Neuronal / chemistry
  • Cell Adhesion Molecules, Neuronal / genetics*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology
  • Glycoproteins / chemistry
  • Glycoproteins / genetics*
  • Membrane Proteins / chemistry
  • Membrane Proteins / genetics
  • Multiprotein Complexes / chemistry
  • Multiprotein Complexes / genetics*
  • Nerve Tissue Proteins / chemistry
  • Nerve Tissue Proteins / genetics
  • Neuromuscular Junction / genetics
  • Neuromuscular Junction / physiology
  • Neuropeptides / chemistry
  • Neuropeptides / genetics*
  • Presynaptic Terminals / chemistry
  • Receptors, Glutamate / genetics
  • Synapses / genetics
  • Synaptic Transmission / genetics
  • Wiskott-Aldrich Syndrome Protein Family / chemistry
  • Wiskott-Aldrich Syndrome Protein Family / genetics

Substances

  • Actins
  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal
  • Glycoproteins
  • Membrane Proteins
  • Multiprotein Complexes
  • Nerve Tissue Proteins
  • Neuropeptides
  • Receptors, Glutamate
  • Wiskott-Aldrich Syndrome Protein Family
  • neurexophilin
  • neuroligin 1
  • neuroligin 2
  • neuroligin 3