Tropomyosin-related tyrosine kinase B (TrkB) is the receptor for brain-derived neurotrophic factor (BDNF) and provides critical signaling that supports the development and function of the mammalian nervous system. Like other receptor tyrosine kinases (RTKs), TrkB is thought to signal as a dimer. Using cell imaging and biochemical assays, we found that TrkB acted as a monomeric receptor at the plasma membrane regardless of its binding to BDNF and initial activation. Dimerization occurred only after the internalization and accumulation of TrkB monomers within BDNF-containing endosomes. We further showed that dynamin-mediated endocytosis of TrkB-BDNF was required for the effective activation of the kinase AKT but not of the kinase ERK1/2. Thus, we report a previously uncharacterized mode of monomeric signaling for an RTK and a specific role for the endosome in TrkB homodimerization.

Tropomyosin相关酪氨酸激酶B（TrkB）是脑源性神经营养因子（BDNF）的受体，并提供支持哺乳动物神经系统发育和功能的关键信号。像其他受体酪氨酸激酶（RTKs）一样，TrkB被认为是二聚体。使用细胞成像和生化分析，我们发现TrkB充当质膜上的单体受体，无论其与BDNF的结合和初始激活如何。仅在TrkB单体在含BDNF的内体中内化和积累后才发生二聚化。我们进一步表明，dynamin介导的TrkB-BDNF的内吞作用是激酶AKT而不是激酶ERK1 / 2的有效激活所必需的。因此，