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Title:Optogenetic Restoration of Abrogated mGluR Signaling in Fragile X Syndrome
Author(s):Ashraf, Humza
Contributor(s):Zhang, Kai
Fragile X Syndrome
Abstract:Fragile X syndrome (FXS) causes exaggerated long term depression (LTD) due to reduction in binding between the Homer protein scaffold and group 1 metabotropic glutamate receptors (mGluRs) in excitatory synapses. Translational dysregulation favors constitutive binding of a short Homer splice variant, H1a, to mGluRs. However, the dynamic interplay between Homer and H1a in regulating synaptic plasticity have yet to be characterized. Here we show that the optogenetic CRY2-CIB1 heterodimerization interaction can be applied to quantitatively titrate Homer binding in vivo. We speculate that recovery from the FXS disease condition can be mimicked via light-inducible membrane recruitment of Homer to mGluR in PC12 cells. Thus, our optogenetic system may have wide applications for more precisely studying dysregulated mGluR signaling associated with disease.
Issue Date:2017
Genre:Dissertation / Thesis
Rights Information:Copyright 2017 Humza Ashraf
Date Available in IDEALS:2017-05-15

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