Howard Hughes Medical Institute and Department of Biology, University of Washington, Seattle, United States.
Institute of Transformative Biomolecules (WPI-ITbM), Nagoya University, Aichi, Japan.
Elife. 2020 Aug 14;9:e58097. doi: 10.7554/eLife.58097.
Receptor endocytosis is important for signal activation, transduction, and deactivation. However, how a receptor interprets conflicting signals to adjust cellular output is not clearly understood. Using genetic, cell biological, and pharmacological approaches, we report here that ERECTA-LIKE1 (ERL1), the major receptor restricting plant stomatal differentiation, undergoes dynamic subcellular behaviors in response to different EPIDERMAL PATTERNING FACTOR (EPF) peptides. Activation of ERL1 by EPF1 induces rapid ERL1 internalization via multivesicular bodies/late endosomes to vacuolar degradation, whereas ERL1 constitutively internalizes in the absence of EPF1. The co-receptor, TOO MANY MOUTHS is essential for ERL1 internalization induced by EPF1 but not by EPFL6. The peptide antagonist, Stomagen, triggers retention of ERL1 in the endoplasmic reticulum, likely coupled with reduced endocytosis. In contrast, the dominant-negative ERL1 remained dysfunctional in ligand-induced subcellular trafficking. Our study elucidates that multiple related yet unique peptides specify cell fate by deploying the differential subcellular dynamics of a single receptor.
受体内化对于信号的激活、转导和失活非常重要。然而，受体如何解释相互冲突的信号来调节细胞输出还不是很清楚。本文采用遗传、细胞生物学和药理学方法，报告了主要限制植物气孔分化的受体 ERECTA-LIKE1（ERL1），在响应不同的 EPIDERMAL PATTERNING FACTOR（EPF）肽时，会发生动态的亚细胞行为。EPF1 激活 ERL1 会通过多泡体/晚期内体快速内化到液泡中进行降解，而在没有 EPF1 的情况下，ERL1 则会持续内化。共受体 TOO MANY MOUTHS 对于 EPF1 诱导的 ERL1 内化是必需的，但对于 EPFL6 则不是必需的。肽拮抗剂 Stomagen 触发 ERL1 在内质网中的滞留，可能与内吞作用的减少有关。相比之下，显性失活的 ERL1 在配体诱导的亚细胞运输中仍然功能失调。我们的研究阐明了多个相关但独特的肽通过部署单个受体的差异亚细胞动力学来指定细胞命运。
