[Abstract Title]. - Society for Neuroscience

Poster
254. Schizophrenia: Mutant Animal Models
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 254.13/Y2
Topic: C.15.d. Schizophrenia: Mutant animal models
Support: NS29071
DK07328
Title: The role of intracellular processing of Type III Neuregulin 1 in cortical development
Authors: *Y. CHEN 1 , M. HANCOCK 1 , D. A. TALMAGE 2 , L. W. ROLE 1 ;
1 Neurobio. and Behavior, 2 Dept. of Pharmacol., SUNY at Stony Brook, New York, NY
Abstract: Neuregulin 1 is a schizophrenia susceptibility gene. Among Neuregulin 1 proteins,
Type III Neuregulin 1 (Nrg1) isoforms differ in their ability to signal in a contact-dependent
manner. Ligand binding and depolarization have been shown to induce an intramembranous, γsecretase
dependent cleavage event resulting in release of the intracellular domain of Nrg1
(Nrg1-ICD) and Nrg1-ICD translocation to the nucleus. Using site-directed mutagenesis, we
have identified amino acid residues in Nrg1 required for γ-secretase-mediated cleavage and
nuclear translocation in CHO cells and cortical neurons. Interestingly, the sequences required for
γ-secretase processing include Valine 321, a residue altered by a polymorphism associated with
increased risk for developing schizophrenia. Furthermore, using mutant forms of Nrg1 defective
in proteolytic cleavage and nuclear localization we are studying whether aberrant intracellular
processing can contribute to cortical dysfunction phenotypes similar to those seen in
schizophrenia.
Disclosures: Y. Chen, None; M. Hancock, None; D.A. Talmage, None; L.W. Role, None.
Poster
254. Schizophrenia: Mutant Animal Models
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 254.14/Y3
Topic: C.15.d. Schizophrenia: Mutant animal models