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PLoS One. 2013 Aug 19;8(8):e72164. doi: 10.1371/journal.pone.0072164. eCollection 2013.

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

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  • 1Molecular Cardiovascular Research, Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany. michael.rohe@mdc-berlin.de

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.

PMID:
23977241
[PubMed - indexed for MEDLINE]
PMCID:
PMC3747043
Free PMC Article
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