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

108 Scopus citations


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
Issue number1
StatePublished - Oct 2 2013
Externally publishedYes

ASJC Scopus subject areas

  • General Neuroscience


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