SORLA-Mediated Trafficking of TrkB Enhances the Response of Neurons to BDNF |
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| Authors: | Michael Rohe Daniela Hartl Anja Nawarecki Fjorback Joachim Klose Thomas E Willnow |
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| Institution: | 1. Molecular Cardiovascular Research, Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany.; 2. Institute for Medical Genetics and Human Genetics, Charité - University Medicine Berlin, Berlin, Germany.; 3. Department of Biomedicine, Aarhus University, Aarhus, Denmark.; University of Louisville, United States of America, |
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| Abstract: | Stimulation of neurons with brain-derived neurotrophic factor (BDNF) results in robust induction of SORLA, an intracellular sorting receptor of the VPS10P domain receptor gene family. However, the relevance of SORLA for BDNF-induced neuronal responses has not previously been investigated. We now demonstrate that SORLA is a sorting factor for the tropomyosin-related kinase receptor B (TrkB) that facilitates trafficking of this BDNF receptor between synaptic plasma membranes, post-synaptic densities, and cell soma, a step critical for neuronal signal transduction. Loss of SORLA expression results in impaired neuritic transport of TrkB and in blunted response to BDNF in primary neurons; and it aggravates neuromotoric deficits caused by low BDNF activity in a mouse model of Huntington’s disease. Thus, our studies revealed a key role for SORLA in mediating BDNF trophic signaling by regulating the intracellular location of TrkB. |
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