Virology: 'Influenzing' the host response


A rare variant of Epac2 that is found in some individuals with autism preferentially affects the basal over the apical dendrites of cortical neurons (PLoS Biol. 10, e1001350). The specificity of this effect suggests that the mutations found in people with autism may result in relatively subtle effects on brain architecture. Epac2 is a brain-enriched guanine nucleotide exchange factor that regulates the function of the small GTPases Rap and Ras. Deepak Srivastava et al. found that knocking down Epac2 in cortical neurons in vitro reduced the size and complexity of their basal dendritic arbors. Overexpressing an autism-associated Epac2-coding variant had a similar effect. Mechanistically, this mutation disrupted the interaction between Epac2 and Ras. Indeed, inhibiting Ras also impaired basal-dendrite architecture. As the number of identified rare coding variants associated with autism increases, it will be of interest to see whether they also result in phenotypes with an equal degree of specificity within a single cell. It will also be important to establish whether the autism-associated Epac2 mutation has a similar effect on neurons from other brain regions and whether there is a developmental window during which the impairment on basal-dendrite architecture can be reversed.—JCL

DOI: 10.1038/nm.2909

Cite this paper

@article{Swami2012VirologyT, title={Virology: 'Influenzing' the host response}, author={Meera Swami}, journal={Nature Medicine}, year={2012}, volume={18}, pages={1192-1192} }