An In Vivo EGF Receptor Localization Screen in Identifies the Ezrin Homolog ERM-1 as a Temporal Regulator of Signaling

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Abnormal signaling by the epidermal growth factor receptor (EGFR) contributes to the development of various human diseases, including different cancer types. One important mechanism that controls intracellular signal transduction is by regulation of the subcellular receptor localization in the signal-receiving cell. We are investigating the regulation of the EGFR homolog LET-23 in the Nematode C. elegans by observing the localization of the EGFR in the epithelial cells of live animals. This approach has allowed us to study the dynamics of receptor trafficking in cells embedded in their natural environment and receiving physiological concentrations of various extracellular signals. In a systematic RNA interference screen, we have identified 81 genes controlling EGFR localization and signaling in different subcellular compartments. One new regulator of EGFR signaling identified in this screen encodes the Ezrin Homolog ERM-1. We show genetic and biochemical evidence indicating that ERM-1 is part of a buffering mechanism to maintain a pool of immobile EGFR in the basolateral membrane compartment of the epithelial cells. This mechanism permits the generation of a long-lasting EGFR signal during multiple rounds of cell divisions. The control of receptor localization is thus necessary for the precise temporal regulation of signal transduction during animal development.

Vyšlo v časopise: An In Vivo EGF Receptor Localization Screen in Identifies the Ezrin Homolog ERM-1 as a Temporal Regulator of Signaling. PLoS Genet 10(5): e32767. doi:10.1371/journal.pgen.1004341
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004341

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