Rohe Michael, Hartl Daniela, Fjorback Anja Nawarecki, Klose Joachim, Willnow Thomas E
Molecular Cardiovascular Research, Max-Delbrueck-Center for Molecular Medicine, Berlin, Germany.
PLoS One. 2013 Aug 19;8(8):e72164. doi: 10.1371/journal.pone.0072164. eCollection 2013.
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.
用脑源性神经营养因子（BDNF）刺激神经元会导致SORLA的强烈诱导，SORLA是VPS10P结构域受体基因家族的一种细胞内分选受体。然而，此前尚未研究过SORLA与BDNF诱导的神经元反应的相关性。我们现在证明，SORLA是原肌球蛋白相关激酶受体B（TrkB）的一种分选因子，它促进这种BDNF受体在突触质膜、突触后致密物和细胞体之间的运输，这是神经元信号转导的关键步骤。SORLA表达缺失导致原代神经元中TrkB的神经突运输受损以及对BDNF的反应减弱；并且它加剧了亨廷顿舞蹈病小鼠模型中由低BDNF活性引起的神经运动缺陷。因此，我们的研究揭示了SORLA在通过调节TrkB的细胞内定位介导BDNF营养信号传导中的关键作用。
