The Specific α-Neurexin Interactor Calsyntenin-3 Promotes Excitatory and Inhibitory Synapse Development

  • Katherine L. Pettem
  • , Daisaku Yokomaku
  • , Lin Luo
  • , Michael W. Linhoff
  • , Tuhina Prasad
  • , Steven A. Connor
  • , Tabrez J. Siddiqui
  • , Hiroshi Kawabe
  • , Fang Chen
  • , Ling Zhang
  • , Gabby Rudenko
  • , Yu Tian Wang
  • , Nils Brose
  • , Ann Marie Craig

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

Perturbations of cell surface synapse-organizing proteins, particularly α-neurexins, contribute to neurodevelopmental and psychiatric disorders. From anunbiased screen, we identify calsyntenin-3 (alcadein-β) as a synapse-organizing protein unique in binding and recruiting α-neurexins, but not β-neurexins. Calsyntenin-3 is present in many pyramidal neurons throughout cortex and hippocampus but is most highly expressed in interneurons. The transmembrane form of calsyntenin-3 can trigger excitatory and inhibitory presynapse differentiation in contacting axons. However, calsyntenin-3-shed ectodomain, which represents about half the calsyntenin-3 pool in brain, suppresses the ability of multiple α-neurexin partners including neuroligin 2 and LRRTM2 to induce presynapse differentiation. Clstn3-/- mice show reductions in excitatory and inhibitory synapse density by confocal and electron microscopy and corresponding deficits in synaptic transmission. These results identify calsyntenin-3 as an α-neurexin-specific binding partner required for normal functional GABAergic and glutamatergic synapse development

Original languageEnglish (US)
Pages (from-to)113-128
Number of pages16
JournalNeuron
Volume80
Issue number1
DOIs
StatePublished - Oct 2 2013
Externally publishedYes

ASJC Scopus subject areas

  • General Neuroscience

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