| Abstract No.: | B-B2047 |
| Country: | Canada |
| | |
| Title: | ERBB4-NEUREGULIN SIGNALING MODULATES SYNAPSE DEVELOPMENT AND DENDRITIC ARBORIZATION THROUGH DISTINCT MECHANISMS |
| | |
| Authors/Affiliations: | 1 Daria Krivosheya, 1 Lucia Tapia, 1 Rochelle Hines, 1 Kun Huang, 1 Joshua Levinson, 2 Annie Ting, 1 Yunhee Kang, 1 Ann Marie Craig,2 Lin Mei;
1 University of British Columbia, BC, Canada; 2 Medical College of Georgia, Augusta, GA, USA |
| | |
| Content: | 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 and is specifically enriched at both excitatory and inhibitory postsynaptic sites. Overexpression of ErbB4 postsynaptically enhances size, but not the number of presynaptic inputs, demonstrating a specific role for ErbB4 in synapse maturation. Using ErbB4 mutant constructs, we demonstrate that this process requires the extracellular domain of ErbB4, while its
tyrosine kinase activity is dispensable for synapse maturation. Moreover,interference with PDZ-mediated interactions reduces ErbB4 synaptic targeting and surface expression, and abolishes its effects on synaptic maturation. We also demonstrate that stimulation of ErbB4 using a soluble form of NRG1 results in aberrant dendritic arborization through activation of the tyrosine kinase domain of ErbB4 and the phosphoinositide-3 kinase (PI3K) pathway. These findings demonstrate that ErbB4/NRG1 signaling differentially regulates synapse maturation and dendritic morphology by two distinct mechanisms involving trans-synaptic signaling and tyrosine kinase activity, respectively.
|
| | |
| Back |
|
