Defective endocytosis and vesicular trafficking of signaling receptors has recently emerged as a multifaceted hallmark of malignant cells. Clathrin-coated pits (CCPs) display highly heterogeneous dynamics on the plasma membrane where they can take from 20 s to over 1 min to form cytosolic coated vesicles. Despite the large number of cargo molecules that traffic through CCPs, it is not well understood whether signaling receptors activated in cancer, such as epidermal growth factor receptor (EGFR), are regulated through a specific subset of CCPs. The signaling lipid phosphatidylinositol (3,4,5)-trisphosphate [PI(3,4,5)P3], which is dephosphorylated by phosphatase and tensin homolog (PTEN), is a potent tumorigenic signaling lipid. By using total internal reflection fluorescence microscopy and automated tracking and detection of CCPs, we found that EGF-bound EGFR and PTEN are enriched in a distinct subset of short-lived CCPs that correspond with clathrin-dependent EGF-induced signaling. We demonstrated that PTEN plays a role in the regulation of CCP dynamics. Furthermore, increased PI(3,4,5)P3 resulted in higher proportion of short-lived CCPs, an effect that recapitulates PTEN deletion. Altogether, our findings provide evidence for the existence of short-lived 'signaling-capable' CCPs.

中文翻译：

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PTEN的丢失会促进具有信号传递能力的网格蛋白包被的凹坑的形成。

缺陷性内吞作用和信号传导受体的囊泡运输最近已成为恶性细胞的多方面标志。网格蛋白包被的凹坑（CCP）在质膜上显示出高度异质的动力学，它们可能需要20 s到1分钟以上的时间才能形成胞质包被的囊泡。尽管有大量货物分子通过CCP进行运输，但尚不清楚如何通过CCP的特定子集来调节癌症中激活的信号受体，例如表皮生长因子受体（EGFR）。信号脂质磷脂酰肌醇（3,4,5）-三磷酸[PI（3,4,5）P3]是一种有效的致瘤信号脂质，被磷酸酶和肌腱蛋白同源物（PTEN）磷酸化。通过使用全内反射荧光显微镜以及对CCP的自动跟踪和检测，我们发现，EGF结合的EGFR和PTEN富含短时CCP的独特子集，这与网格蛋白依赖性EGF诱导的信号传导相对应。我们证明了PTEN在CCP动力学调节中起作用。此外，增加的PI（3,4,5）P3导致更高比例的短命CCP，这一现象概括了PTEN缺失。总之，我们的发现为存在短暂的“具有信号功能”的CCP提供了证据。