Review ARTICLE

Front. Synaptic Neurosci., 26 January 2011 | doi: 10.3389/fnsyn.2011.00001

Synaptic signaling and aberrant RNA splicing in autism spectrum disorders

  • 1 Program in Pharmacogenomics, Department of Pharmacology, The Ohio State University, Columbus, OH, USA
  • 2 Division of Human Genetics, Department of Pharmacology, Psychiatry, College of Medicine and College of Pharmacy, The Ohio State University, Columbus, OH, USA

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.

Keywords: autism spectrum disorder, synaptogenesis, alternative RNA splicing, cellular adhesion molecules, neurexin, neuroligin, gene expression, neural development

Citation: Smith RM and Sadee W (2011) Synaptic signaling and aberrant RNA splicing in autism spectrum disorders. Front. Syn. Neurosci. 3:1. doi: 10.3389/fnsyn.2011.00001

Received: 25 April 2010; Accepted: 12 January 2011;
Published online: 26 January 2011.

Edited by:

Kelsey Martin, University of California Los Angeles, USA

Reviewed by:

Peter Scheiffele, University of Basel, Switzerland
Kelsey Martin, University of California Los Angeles, USA

Copyright: © 2011 Smith and Sadee. This is an open-access article subject to an exclusive license agreement between the authors and Frontiers Media SA, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited.

*Correspondence: Wolfgang Sadee, Department of Pharmacology, The Ohio State University, 333 West 10th Avenue, 5072 Graves Hall, Columbus, OH 43210, USA. e-mail: wolfgang.sadee@osumc.edu

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