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

KatherineL Pettem, Daisaku Yokomaku, Lin Luo, MichaelW Linhoff, Tuhina Prasad, StevenA Connor, TabrezJ Siddiqui, Hiroshi Kawabe, Fang Chen, Ling Zhang, Gabrielle Rudenko, YuTian Wang, Nils Brose, AnnMarie Craig

Research output: Contribution to journalArticle

76 Citations (Scopus)

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

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Synapses
Aptitude
Pyramidal Cells
Sexual Partners
Interneurons
Confocal Microscopy
Synaptic Transmission
Psychiatry
Axons
Hippocampus
Electron Microscopy
Proteins
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Pettem, K., Yokomaku, D., Luo, L., Linhoff, M., Prasad, T., Connor, S., ... Craig, A. (2013). The Specific α-Neurexin Interactor Calsyntenin-3 Promotes Excitatory and Inhibitory Synapse Development. Neuron, 80(1), 113-128. https://doi.org/10.1016/j.neuron.2013.07.016

The Specific α-Neurexin Interactor Calsyntenin-3 Promotes Excitatory and Inhibitory Synapse Development. / Pettem, KatherineL; Yokomaku, Daisaku; Luo, Lin; Linhoff, MichaelW; Prasad, Tuhina; Connor, StevenA; Siddiqui, TabrezJ; Kawabe, Hiroshi; Chen, Fang; Zhang, Ling; Rudenko, Gabrielle; Wang, YuTian; Brose, Nils; Craig, AnnMarie.

In: Neuron, Vol. 80, No. 1, 02.10.2013, p. 113-128.

Research output: Contribution to journalArticle

Pettem, K, Yokomaku, D, Luo, L, Linhoff, M, Prasad, T, Connor, S, Siddiqui, T, Kawabe, H, Chen, F, Zhang, L, Rudenko, G, Wang, Y, Brose, N & Craig, A 2013, 'The Specific α-Neurexin Interactor Calsyntenin-3 Promotes Excitatory and Inhibitory Synapse Development', Neuron, vol. 80, no. 1, pp. 113-128. https://doi.org/10.1016/j.neuron.2013.07.016
Pettem, KatherineL ; Yokomaku, Daisaku ; Luo, Lin ; Linhoff, MichaelW ; Prasad, Tuhina ; Connor, StevenA ; Siddiqui, TabrezJ ; Kawabe, Hiroshi ; Chen, Fang ; Zhang, Ling ; Rudenko, Gabrielle ; Wang, YuTian ; Brose, Nils ; Craig, AnnMarie. / The Specific α-Neurexin Interactor Calsyntenin-3 Promotes Excitatory and Inhibitory Synapse Development. In: Neuron. 2013 ; Vol. 80, No. 1. pp. 113-128.
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