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Cell receptors can be picky partners

G protein-coupled receptors, GPCRs for short, are the largest family of human cell-surface receptors and regulate an incredible range of body functions, from sensation to growth and hormone responses. A subfamily of GPCRs is targeted by opioids, a class of drugs frequently used as pain relievers but causing severe side-effects. GPCRs can trigger different physiological responses depending on which molecule is binding to the receptor, but the exact underlying mechanisms are unknown.

 

Real-time observations in living cells

In a recent study published in the eLIFE Journal, Prof. Miriam Stoeber and colleagues have been able to directly detect the GPCR’s preference for binding to different cellular proteins without interfering with the signaling process. These experiments allowed the scientists to show in living cells that the identity of the signaling molecule affects which protein will bind to the GPCR upon activation. Their study conveys that GPCRs can not only communicate that a signaling molecule is binding – but that they can respond differently to convey what molecule it is more specifically.

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Adapted from a kymograph traced inside the cell, depicting pseudocolored fluorescence intensities. © Stoeber et al. (CC BY 4.0)

 

What’s next?

Understanding the way GPCRs communicate information about the binding of a molecule might help to improve opioid drugs in order to direct their signaling towards the desired response while reducing unwanted side-effects. The newly arrived team of Prof. Miriam Stoeber is seeking to better understand the differences between the mode of action of endogenous opioid peptides and opioid drugs used as pain relievers.

March 4, 2020
  News