Stimulated ErbB4 internalization is necessary for neuregulin signaling in neurons |
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Authors: | Liu Yu Tao Yan-Mei Woo Ran-Sook Xiong Wen-Cheng Mei Lin |
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Affiliation: | Program of Developmental Neurobiology, Institute of Molecular Medicine and Genetics, Department of Neurology, Medical College of Georgia, Augusta, GA 30912, USA. |
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Abstract: | Neuregulin-1 (NRG1) plays an important role in neural development, synapse formation, and synaptic plasticity by activating ErbB receptor tyrosine kinases. Although ligand-induced endocytosis has been shown to be important for many receptor tyrosine kinases, whether NRG1 signaling depends on ErbB endocytosis remains controversial. Here, we provide evidence that ErbB4, a prominent ErbB protein in the brain, becomes internalized in NRG1-stimulated neurons. The induced ErbB4 endocytosis requires its kinase activity. Remarkably, inhibition of ErbB endocytosis attenuates NRG1-induced activation of Erk and Akt in neurons. These observations indicate a role of ErbB endocytosis in NRG1 signaling in neurons. |
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Keywords: | ErbB4 Tyrosine kinase Neuregulin Internalization Endocytosis Biotinylation Neurons Schizophrenia |
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