Dendritic ‘translatome’ in fragile X syndrome and autism

  • Awarded: 2014
  • Award Type: Explorer
  • Award #: 324586

Our species’ remarkable cognitive, perceptive and motor capabilities depend on the formation, maturation and maintenance of neuronal connectivity in the brain. Miswiring or dysfunction of neural circuits can lead to psychiatric disorders, including autism, that affect some of the most distinctly human cognitive functions.

Neural circuits are assembled through synapses, or connections between neurons — highly polarized nerve cells that contain, at their center, a cell body from which long projections emanate. These projections include dendrites, which receive information from presynaptic neurons, and axons, which transmit information to postsynaptic neurons. The synthesis of proteins from the translation of messenger RNA transcripts takes place mostly within the neuronal cell body. Within dendrites, however, proteins are also synthesized locally in order to provide a means to regulate protein content at or near sites of synaptic contact.

Mechanistic studies have implicated alterations in protein translation, dendritic morphology and synaptic function in the pathogenesis of fragile X syndrome(a syndromic form of autism) and other autism spectrum disorders. The specific roles of intra-dendritic translation in these disorders, however, have not been extensively explored.

Kenneth Kwan and his colleagues at the University of Michigan are pioneering a technique to study dendritic protein synthesis. Using animal models of fragile X syndrome and other autism spectrum disorders, the team seeks to identify and characterize dendritic transcripts important in these disorders. They hope this work will reveal new candidate mechanisms underlying the dendritic dysfunction in the disorders. It may also have the potential to lead to new molecular targets for therapy.

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