Interplay of Endocytosis and Growth Factor Receptor Signalling.
Interplay of Endocytosis and Growth Factor Receptor Signalling.
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DOI：
10.1007/978-3-319-96704-2_7
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发表时间：
2018
影响因子：
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通讯作者：
Rachel E. Moore;M. G. Pujol;Zhou Zhu;E. Smythe
中科院分区：
文献类型：
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作者：
Rachel E. Moore;M. G. Pujol;Zhou Zhu;E. Smythe
生长因子受体在胚胎发育和成人体内平衡中起着多种作用。这些受体在不同的细胞环境中反复激活，并产生不同的细胞结果。这就引出了一个问题，即在特定的发育、空间和时间背景下，或在成人组织中，细胞如何解释生长因子受体的信号传导，以提供质量上不同的信号传导输出。这可能发生的一种机制是通过内吞调节。内吞作用在生长因子受体信号传导中的作用的原始范例是受体摄取通过减少可用于活化的细胞表面受体的数量和靶向活化的受体进行降解而在信号传导中具有定量作用。然而，在过去几年中，在许多不同的实验系统中，一系列研究已经证明了内吞转运在受体信号传导中的额外定性作用，具体结果取决于信号传导复合物的位置。内体内受体的限制可以在空间上调节信号传导，促进特定蛋白质相互作用或在整个运输过程中改变的翻译后修饰。因此，内吞作用并不简单地调节细胞表面表达，而是严格控制蛋白质相互作用和功能以产生不同的结果。
Growth factor receptors play a variety of roles during embryonic development and in adult homeostasis. These receptors are activated repeatedly in different cellular contexts and with different cellular outcomes. This begs the question as to how cells in a particular developmental, spatial and temporal context, or in adult tissue, interpret signalling by growth factor receptors in order to deliver qualitatively different signalling outputs. One mechanism by which this could occur is via endocytic regulation. The original paradigm for the role of endocytosis in growth factor receptor signalling was that receptor uptake has a quantitative role in signalling by reducing the number of cell surface receptors available for activation and targeting activated receptors for degradation. However, a range of studies over the last several years, in many different experimental systems, has demonstrated an additional qualitative role for endocytic trafficking in receptor signalling, with specific outcomes depending on the location of the signalling complex. Confinement of receptors within endosomes can spatially regulate signalling, facilitating specific protein interactions or post-translational modifications that alter throughout the trafficking process. Therefore, endocytosis does not simply regulate cell surface expression, but tightly controls protein interactions and function to produce distinct outcomes.