Sorting of EGF and transferrin at the plasma membrane and by cargo-specific signaling to EEA1-enriched endosomes.
Sorting of EGF and transferrin at the plasma membrane and by cargo-specific signaling to EEA1-enriched endosomes.
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将EGF和转铁蛋白分选在质膜上，并通过货物特异性信号传导向EEA1富集的内体。
DOI：
10.1242/jcs.031484
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发表时间：
2008-10-15
影响因子：
4
通讯作者：
Corvera S
中科院分区：
文献类型：
--
作者：
Leonard D;Hayakawa A;Lawe D;Lambright D;Bellve KD;Standley C;Lifshitz LM;Fogarty KE;Corvera S
受体的生物学功能取决于它们通过内体途径的适当运输。内化后，转铁蛋白 (Tf) 受体定量循环至质膜，而表皮生长因子 (EGF) 受体则发生降解。为了确定 Tf 和 EGF 如何参与这两种不同的途径，我们使用 TIRF-M（全内反射荧光显微镜）对它们在活细胞中的结合和早期内吞途径进行成像。我们发现 EGF 和 Tf 结合到不同的质膜区域，并掺入不同的内吞囊泡中。内化后，富含 EGF 和 Tf 的囊泡与含有 EEA1（早期内体抗原 1）的内体相互作用。 EGF 被掺入并保留在这些内体中，而含有 Tf 的囊泡迅速解离并移动到核旁区室。携带 EGF 的内吞囊泡比携带 Tf 的内吞囊泡募集更多的 Rab5 GTPase，通过加强它们与富含 EEA1 的内体的关联，可能为观察到的货物特异性分选提供一种机制。这些结果揭示了 Tf 和 EGF 的内吞前分选、富含 EEA1 的内质在 EGF 运输中的特殊作用，以及这些内吞体对内吞囊泡进行货物特异性分选的潜在机制。
The biological function of receptors is determined by their appropriate trafficking through the endosomal pathway. Following internalization, the transferrin (Tf) receptor quantitatively recycles to the plasma membrane, while the epidermal growth factor (EGF) receptor undergoes degradation. To determine how Tf and EGF engage these two different pathways we imaged their binding and early endocytic pathway in live cells using TIRF-M (Total Internal Reflection Fluorescence Microscopy). We find that EGF and Tf bind to distinct plasma membrane regions, and are incorporated into different endocytic vesicles. After internalization both EGF-enriched and Tf-enriched vesicles interact with endosomes containing EEA1 (Early Endosome Antigen-1). EGF is incorporated and retained in these endosomes, while Tf-containing vesicles rapidly dissociate and move to a juxtanuclear compartment. Endocytic vesicles carrying EGF recruit more Rab5 GTPase than those carrying Tf, which by strengthening their association with EEA1-enriched endosomes may provide a mechanism for the observed cargo-specific sorting. These results reveal pre-endocytic sorting of Tf and EGF, a specialized role for EEA1-enriched endosmes in EGF trafficking, and a potential mechanism for cargo-specified sorting of endocytic vesicles by these endosomes.