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 tropomyosinrelated kinase receptor B (TrkB) that facilitates trafficking of this BDNF receptor between synaptic plasma membranes, postsynaptic 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.
Rohe, M., Hartl, D., Fjorback, A. N., Klose, J., & Willnow, T. E. (2013). SORLA-mediated trafficking of TrkB enhances the response of neurons to BDNF. PLoS ONE, 8(8). https://doi.org/10.1371/journal.pone.0072164