Document Detail


ErbB4-neuregulin signaling modulates synapse development and dendritic arborization through distinct mechanisms.
MedLine Citation:
PMID:  18819924     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Perturbations in neuregulin-1 (NRG1)/ErbB4 function have been associated with schizophrenia. Affected patients exhibit altered levels of these proteins and display hypofunction of glutamatergic synapses as well as altered neuronal circuitry. However, the role of NRG1/ErbB4 in regulating synapse maturation and neuronal process formation has not been extensively examined. Here we demonstrate that ErbB4 is expressed in inhibitory interneurons at both excitatory and inhibitory postsynaptic sites. Overexpression of ErbB4 postsynaptically enhances size but not number of presynaptic inputs. Conversely, knockdown of ErbB4 using shRNA decreases the size of presynaptic inputs, demonstrating a specific role for endogenous ErbB4 in synapse maturation. Using ErbB4 mutant constructs, we demonstrate that ErbB4-mediated synapse maturation requires its extracellular domain, whereas its tyrosine kinase activity is dispensable for this process. We also demonstrate that depletion of ErbB4 decreases the number of primary neurites and that stimulation of ErbB4 using a soluble form of NRG1 results in exuberant dendritic arborization through activation of the tyrosine kinase domain of ErbB4 and the phosphoinositide 3-kinase pathway. These findings demonstrate that NRG1/ErbB4 signaling differentially regulates synapse maturation and dendritic morphology via two distinct mechanisms involving trans-synaptic signaling and tyrosine kinase activity, respectively.
Authors:
Daria Krivosheya; Lucia Tapia; Joshua N Levinson; Kun Huang; Yunhee Kang; Rochelle Hines; Annie K Ting; Ann Marie Craig; Lin Mei; Shernaz X Bamji; Alaa El-Husseini
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-09-26
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  283     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2008 Nov 
Date Detail:
Created Date:  2008-11-17     Completed Date:  2009-01-22     Revised Date:  2014-09-21    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  32944-56     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
COS Cells
Cercopithecus aethiops
Dendrites / metabolism
Hippocampus / metabolism
Humans
Mice
Models, Biological
Neuregulins / metabolism*
Neurons / metabolism
Phosphatidylinositol 3-Kinases / metabolism
Rats
Receptor, Epidermal Growth Factor / metabolism*
Signal Transduction*
Synapses / metabolism
Grant Support
ID/Acronym/Agency:
R01 MH070860/MH/NIMH NIH HHS; R01 MH070860-02/MH/NIMH NIH HHS; R01 MH070860-03/MH/NIMH NIH HHS; R01 MH083317/MH/NIMH NIH HHS; R21 MH083563/MH/NIMH NIH HHS
Chemical
Reg. No./Substance:
0/Neuregulins; EC 2.7.1.-/Phosphatidylinositol 3-Kinases; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.10.1/receptor tyrosine-protein kinase erbB-4

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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