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SORLA-mediated trafficking of TrkB enhances the response of neurons to BDNF

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Item Type:Article
Title:SORLA-mediated trafficking of TrkB enhances the response of neurons to BDNF
Creators Name:Rohe, M. and Hartl, D. and Fjorback, A.N. and Klose, J. and Willnow, T.E.
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.
Keywords:Animal Disease Models, Brain-Derived Neurotrophic Factor, Cell Line, Gene Expression Regulation, Huntington Disease, LDL Receptors, LDL-Receptor Related Proteins, Membrane Glycoproteins, Membrane Transport Proteins, Neurons, Newborn Animals, Primary Cell Culture, Protein Transport, Protein-Tyrosine Kinases, Signal Transduction, Synapses, Transgenic Mice, Animals, Mice
Source:PLoS ONE
Publisher:Public Library of Science
Page Range:e72164
Date:19 August 2013
Official Publication:https://doi.org/10.1371/journal.pone.0072164
PubMed:View item in PubMed

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