A novel endocytic recycling signal distinguishes biological responses of Trk neurotrophin receptors
A novel endocytic recycling signal distinguishes biological responses of Trk neurotrophin receptors
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DOI：
10.1091/mbc.e05-07-0651
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发表时间：
2005-12-01
影响因子：
3.3
通讯作者：
Lee, FS
中科院分区：
文献类型：
--
作者：
Chen, ZY;Ieraci, A;Lee, FS
已显示信号受体向交替细胞内途径的内吞运输导致不同的生物学后果。在这项研究中，我们报告说，两个神经营养因子受体（原肌球蛋白相关激酶TrkA和TrkB）绑定到各自的配体（神经生长因子和脑源性神经营养因子）后，穿越不同的内吞途径。我们提供的证据表明，神经分泌细胞和神经元中的TrkA受体主要以配体依赖性方式回收到细胞表面。我们已经确定了一个特定的序列中的TrkA质膜区域，这是不同的TrkB受体，是必要的和足够的快速回收的内化受体。相反，TrkB受体主要被分选到降解途径。将TrkA再循环序列移植到TrkB受体中将TrkB受体重新路由到再循环途径。最后，我们将这些不同的贩运途径与替代生物反应联系起来。与TrkB受体相比，在长期的神经营养因子治疗中，TrkA受体产生磷脂酰肌醇3-激酶/Akt信号传导的长期激活以及存活应答。这些结果表明，TrkA受体，主要回收信号依赖性的方式，具有独特的生物学特性，由其特定的内吞运输行程。
Endocytic trafficking of signaling receptors to alternate intracellular pathways has been shown to lead to diverse biological consequences. In this study, we report that two neurotrophin receptors (tropomyosin-related kinase TrkA and TrkB) traverse divergent endocytic pathways after binding to their respective ligands (nerve growth factor and brain-derived neurotrophic factor). We provide evidence that TrkA receptors in neurosecretory cells and neurons predominantly recycle back to the cell surface in a ligand-dependent manner. We have identified a specific sequence in the TrkA juxtamembrane region, which is distinct from that in TrkB receptors, and is both necessary and sufficient for rapid recycling of internalized receptors. Conversely, TrkB receptors are predominantly sorted to the degradative pathway. Transplantation of the TrkA recycling sequence into TrkB receptors reroutes the TrkB receptor to the recycling pathway. Finally, we link these divergent trafficking pathways to alternate biological responses. On prolonged neurotrophin treatment, TrkA receptors produce prolonged activation of phosphatidylinositol 3-kinase/Akt signaling as well as survival responses, compared with TrkB receptors. These results indicate that TrkA receptors, which predominantly recycle in signal-dependent manner, have unique biological properties dictated by its specific endocytic trafficking itinerary.