Candidate autism gene screen identifies critical role for cell-adhesion molecule CASPR2 in dendritic arborization and spine development

Garret R. Anderson, Timothy Galfin, Wei Xu, Jason Aoto, Robert C. Malenka, Thomas C. Südhof

Research output: Contribution to journalArticlepeer-review

124 Scopus citations

Abstract

Mutations in the contactin-associated protein 2 (CNTNAP2) gene encoding CASPR2, a neurexin-related cell-adhesion molecule, predispose to autism, but the function of CASPR2 in neural circuit assembly remains largely unknown. In a knockdown survey of autism candidate genes, we found that CASPR2 is required for normal development of neural networks. RNAi-mediated knockdown of CASPR2 produced a cell-autonomous decrease in dendritic arborization and spine development in pyramidal neurons, leading to a global decline in excitatory and inhibitory synapse numbers and a decrease in synaptic transmission without a detectable change in the properties of these synapses. Our data suggest that in addition to the previously described role of CASPR2 in mature neurons, where CASPR2 organizes nodal microdomains of myelinated axons, CASPR2 performs an earlier organizational function in developing neurons that is essential for neural circuit assembly and operates coincident with the time of autism spectrum disorder (ASD) pathogenesis.

Original languageEnglish (US)
Pages (from-to)18120-18125
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume109
Issue number44
DOIs
StatePublished - Oct 30 2012

Keywords

  • Dendrite
  • Synaptogenesis

ASJC Scopus subject areas

  • General

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