Schizophrenia Research Forum - A Catalyst for Creative Thinking
Home Profile Membership/Get Newsletter Log In Contact Us
 For Patients & Families
What's New
Recent Updates
SRF Papers
Current Papers
Search All Papers
Search Comments
News
Research News
Conference News
Plain English
Forums
Current Hypotheses
Idea Lab
Online Discussions
Virtual Conferences
Interviews
Resources
What We Know
SchizophreniaGene
Animal Models
Drugs in Trials
Research Tools
Grants
Jobs
Conferences
Journals
Community Calendar
General Information
Community
Member Directory
Researcher Profiles
Institutes and Labs
About the Site
Mission
History
SRF Team
Advisory Board
Support Us
How to Cite
Fan (E)Mail
The Schizophrenia Research Forum web site is sponsored by the Brain and Behavior Research Foundation and was created with funding from the U.S. National Institute of Mental Health.
Annotation

Pitcher GM, Kalia LV, Ng D, Goodfellow NM, Yee KT, Lambe EK, Salter MW. Schizophrenia susceptibility pathway neuregulin 1-ErbB4 suppresses Src upregulation of NMDA receptors. Nat Med . 2011 Apr ; 17(4):470-8. PubMed Abstract

Comments on Paper and Primary News
Comment by:  Amanda Jayne Law, SRF Advisor
Submitted 20 April 2011 Posted 20 April 2011

The study by Pitcher and colleagues incorporates a series of well-designed in-vitro experiments aimed at investigating the proposed link between NRG1-ErbB4 signaling, NMDAR activity, and synaptic function. Using wild-type and ErbB4 mutant mice (ErbB4-/-Her4heart), plus pharmacological inhibition of ErbB receptors, the study demonstrates that NRG1 signaling, via ErbB4, suppresses enhancement of NMDA receptors (NMDAR) via inhibition of the Src kinase, Src. Consistent with previous studies (see references 32-37 of Pitcher et al.), the authors demonstrate that NRG1 prevents induction of theta burst-induced LTP (tbLTP), and provide novel data to suggest that this requires Src. Mechanistically, the authors demonstrate that NRG1 is inhibitory to NMDAR EPSCs via blockade of Src. Activation of Src, via EPQ stimulation, results in increased NMDAR EPSC amplitudes; however, pretreatment of slices with soluble NRG1 prior to EPQ blocks the effects of EPQ on NMDAR EPSCs. Convincingly, the authors show that ErbB4 genetic deletion prevents the inhibitory effects of NRG1 on EPQ...  Read more


View all comments by Amanda Jayne Law

Primary News: Neuregulin and ErbB4: Synaptic Jacks of All Trades

Comment by:  Michael CahillPeter Penzes
Submitted 29 April 2011 Posted 29 April 2011
  I recommend this paper

The recent study by Pitcher et al. provides a novel mechanism linking NRG1/ErbB4 activity to the suppression of NMDAR activity in a manner requiring Src kinase inhibition. The study uses biochemical manipulation of Src activation, as well as studies on cells lacking Src, to examine the role for Src kinase on the effects of NRG1 on NMDAR responses in pyramidal neurons. Overall, the study provides convincing evidence indicating that Src inhibition by NRG1 is an important contributor to the effects of NRG1 on NMDAR pyramidal neuronal hypofunction. The effect of NRG1 and ErbB4 on Src family kinase activation remains complex. Previous studies have found that NRG1 can activate Src, and that inhibition of Src family kinases can block some of the effects of NRG1 on cells, including cellular migration and proliferation (Eckert et al., 2009; Grossmann et al., 2009). Moreover, ErbB4 activity is able to activate fyn when overexpressed in heterologous cells, and NRG1 treatment activates fyn in...  Read more


View all comments by Michael Cahill
View all comments by Peter Penzes
Submit a Comment on this Paper
Make a comment on this paper. 

If you already are a member, please login.
Not sure if you are a member? Search our member database.

*First Name  
*Last Name  
Affiliation  
Country or Territory  
*Login Email Address  
*Confirm Email Address  
*Password  
*Confirm Password  
Remember my Login and Password?  
Get SRF newsletter with recent commentary?  
 
Enter the code as it is shown below:
This code helps prevent automated registrations.

I recommend this paper

Please note: A member needs to be both registered and logged in to submit a comment.

Comment:

(If coauthors exist for this comment, please enter their names and email addresses at the end of the comment.)

References:


 
 
SRF News
SRF Comments
Text Size
Reset Text Size
Email this pageEmail this page

Share/Bookmark
 
Copyright © 2005- 2014 Schizophrenia Research Forum Privacy Policy Disclaimer Disclosure Copyright