[Abstract Title]. - Society for Neuroscience

Poster
239. Structural Plasticity at Synapses I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 239.3/D72
Topic: B.08.i. Structural plasticity
Support: NIH grant MH 071316
AHA
NARSAD
NAAR
Title: Autism-associated protein Epac2 promotes synapse destabilization and depression
Authors: *K. WOOLFREY 1 , H. PHOTOWALA 1 , M. YAMASHITA 2 , M. V. BARBOLINA 3 ,
D. P. SRIVASTAVA 1 , M. E. CAHILL 1 , Z. XIE 1 , K. A. JONES 1 , L. A. QUILLIAM 4 , M.
PRAKRIYA 2 , P. PENZES 1 ;
1 Physiol., 2 Mol. Pharmacol. and Biol. Chem., 3 Chem. and Biol. Engin., Northwestern Univ.,
Chicago, IL; 4 Biochem. and Mol. Biol., Indiana Univ. Sch. of Med., Indianapolis, IN
Abstract: Tight regulation of synapse assembly and structure is essential for cortical
development and plasticity, and dysregulation of these processes can result in a variety of
cognitive disorders, including the autism spectrum disorders (ASD). However, much remains
unknown about the molecular mechanisms underlying synapse development and maturation and
how they go awry in disease states. Genetic association studies have identified a number of genes
associated with the autistic phenotype, many of which encode synaptic proteins. We have
focused on one of these proteins, Epac2, which is a PKA-independent cAMP target and Rapguanine-nucleotide
exchange factor (GEF). We report that Epac2 activation induces spine
shrinkage, increases spine motility, reduces synaptic GluR2/3-containing AMPA receptors, and
depresses excitatory transmission, effects blocked by Epac2 knockdown. Importantly, Epac2 also
complexes with Neuroligins and Shank3, synaptic proteins previously implicated in the autistic
phenotype. Collectively, these data identify a novel mechanism that promotes destabilization and
depression of spiny synapses, malfunctioning of which may contribute to cortical dysfunction in
ASD.
Disclosures: K. Woolfrey , None; H. Photowala, None; M. Yamashita, None; M.V.
Barbolina, None; D.P. Srivastava, None; M.E. Cahill, None; Z. Xie, None; L.A. Quilliam,
None; K.A. Jones, None; P. Penzes, None; M. Prakriya, None.