January Newsletter: The GEF Trio and Its Role in Autism Spectrum Disorders

Intellectual disabilities (e.g., neurodevelopmental disorders, autism spectrum disorders [ASDs]) are associated with abnormal development of dendrites and dendritic spines. ASDs are a complex set of behaviorally defined disorders, characterized by impairments in social interaction, communication, and restricted or stereotyped behaviors. Recent studies estimate that 1% of the world-wide population has an ASD1. Dendritic spines are comprised of F-actin and the structural and functional plasticity of spines depend upon the dynamic regulation of actin by Rho-family GTPases. Indeed, Rac and PAK effector proteins are essential regulators of normal brain development and function, including dendritic spine initiation, elongation, and branching2-4. Recent genetic studies revealed that individuals with intellectual disabilities express mutated versions of genes involved in Rho-family GTPase signaling such as a Rho-family GTPase activating protein (GAP), the serine/threonine kinase PAK3, and the Rac/Cdc42 guanine exchange factor (GEF) aPIX5. In addition, the PAK inhibitor FRAX486 is an effective treatment for fragile X syndrome (FXS), the most common inherited form of autism and cognitive disability. FRAX486 reversed dendritic spine and behavioral abnormalities in an in vivo model of FXS6. Moreover, Rac1 activation or inhibition of cofilin, an actin depolymerizing protein, rescues ASD-like phenotypes in Shank3 knock-out mice, an in vivo model of ASDs7-12.

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 Also included in this newsletter:

  • GTPase Assay Kits, Spirochrome™ Live Cell Imaging Probes, GEF Proteins, and more
  • Related Publications