Synaptic signaling and aberrant RNA splicing in autism spectrum disorders

  • Smith R
  • Sadee W
  • 52

    Readers

    Mendeley users who have this article in their library.
  • 13

    Citations

    Citations of this article.

Abstract

Interactions between presynaptic and postsynaptic cellular adhesion molecules (CAMs) drive synapse maturation during development. These trans-synaptic interactions are regulated by alternative splicing of CAM RNAs, which ultimately determines neurotransmitter phenotype. The diverse assortment of RNAs produced by alternative splicing generates countless protein isoforms necessary for guiding specialized cell-to-cell connectivity. Failure to generate the appropriate synaptic adhesion proteins is associated with disrupted glutamatergic and gamma-aminobutyric acid signaling, resulting in loss of activity-dependent neuronal plasticity, and risk for developmental disorders, including autism. While the majority of genetic mutations currently linked to autism are rare variants that change the protein-coding sequence of synaptic candidate genes, regulatory polymorphisms affecting constitutive and alternative splicing have emerged as risk factors in numerous other diseases, accounting for an estimated 40-60% of general disease risk. Here, we review the relationship between aberrant RNA splicing of synapse-related genes and autism spectrum disorders.

Author-supplied keywords

  • Alternative RNA splicing
  • Autism spectrum disorder
  • Cellular adhesion molecules
  • Gene expression
  • Neural development
  • Neurexin
  • Neuroligin
  • Synaptogenesis

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document

Authors

  • Ryan M. Smith

  • Wolfgang Sadee

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free