PerspectiveCell Biology

Keeping in touch with the ER network

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Science  12 May 2017:
Vol. 356, Issue 6338, pp. 584-585
DOI: 10.1126/science.aan4807

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Summary

The epidermal growth factor receptor (EGFR) has fundamental roles in physiology and cancer. It is rapidly internalized (endocytosed) from the cell surface upon ligand binding and activation and can either sustain its signaling by being recycled back to the plasma membrane or get delivered to the lysosome where it is degraded (1). After much debate, it is currently thought that EGFR endocytosis involves clathrin-mediated (CME) and nonclathrin (NCE) mechanisms depending on the ligand concentration and cellular context, with the molecular details of the latter route poorly defined (1, 2). On page 617 of this issue, Caldieri et al. (3) report that the NCE pathway involves transient endoplasmic reticulum (ER)–plasma membrane contacts formed close to the sites of EGFR internalization.