folder

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

Authors

  • M. Rohe
  • D. Hartl
  • A.N. Fjorback
  • J. Klose
  • T.E. Willnow

Journal

  • PLoS ONE

Citation

  • PLoS ONE 8 (8): e72164

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.


DOI

doi:10.1371/journal.pone.0072164