New insights into receptor balancing

fluorescence image of receptor degredation
EGF receptors in the cell membrane in blue and the endosomal structures that internalise and degrade a substantial fraction of them in yellow. IMAGE: EMBL/Pepperkok lab

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Inducible mechanism found by EMBL scientists links receptor degradation and replenishment

Research at EMBL suggests a new mechanism for managing the number of receptors at the cell’s plasma membrane. Receptors on a cell’s membrane detect cues in its environment, and often carry those cues into the cell, triggering chain reactions that enable the cell to respond. For the first time, EMBL scientists have shown an inducible link between the mechanism for degrading these receptors and the process of transporting newly synthesised receptors to the cell surface, to keep the right balance. It is the balance between how many of the receptors are being made, how many are being degraded and how many that are being recycled that determine the number on the cell surface.

A chance conversation got PhD student Sandra Scharaw thinking about the proteins involved in the receptor protein balance in a new way. After exposing the cells to epithelial growth factor (EGF) to induce EGF receptor signalling and as a consequence its partial degradation, Scharaw was surprised to also measure an increase in the production of EGF receptor proteins, as well as the specific machinery to transport it to the cell surface.

The EGF receptor has, in team leader Rainer Pepperkok’s words, been ‘studied to death’, making it an ideal model to study. After revealing a mechanism to maintain EGF receptor number on the cell surface, now the group wonder if there might be other linked feedback loops, especially as the number of receptors on the cell surface also has implications in cancer.