Pumping the brakes: suppression of synapse development by MDGA-neuroligin interactions

Curr Opin Neurobiol. 2019 Aug;57:71-80. doi: 10.1016/j.conb.2019.01.002. Epub 2019 Feb 14.

Abstract

Synapse development depends on a dynamic balance between synapse promoters and suppressors. MDGAs, immunoglobulin superfamily proteins, negatively regulate synapse development through blocking neuroligin-neurexin interactions. Recent analyses of MDGA-neuroligin complexes revealed the structural basis of this activity and indicate that MDGAs interact with all neuroligins with differential affinities. Surprisingly, analyses of mouse mutants revealed a functional divergence, with targeted mutation of Mdga1 and Mdga2 elevating inhibitory and excitatory synapses, respectively, on hippocampal pyramidal neurons. Further research is needed to determine the synapse-specific organizing properties of MDGAs in neural circuits, which may depend on relative levels and subcellular distributions of each MDGA, neuroligin and neurexin. Behavioral deficits in Mdga mutant mice support genetic links to schizophrenia and autism spectrum disorders and raise the possibility of harnessing these interactions for therapeutic purposes.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Adhesion Molecules, Neuronal
  • Dansyl Compounds
  • Galactosamine / analogs & derivatives
  • Mice
  • Nerve Tissue Proteins
  • Synapses*

Substances

  • Cell Adhesion Molecules, Neuronal
  • Dansyl Compounds
  • Nerve Tissue Proteins
  • methyl-N-dansylgalactosaminide
  • Galactosamine