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Nobel Prize in chemistry goes to 2 Americans studying body's receptors

October 10, 2012|By Jon Bardin
  • Robert J. Lefkowitz and Brian K. Kobilka are announced as the winners of the Nobel Prize in chemistry for their work on cellular receptors.
Robert J. Lefkowitz and Brian K. Kobilka are announced as the winners of… (Jonathan Nackstrand / AFP/Getty…)

American scientists Brian K. Kobilka and Robert J. Lefkowitz won the Nobel Prize in chemistry on Wednesday, receiving the honor for their work unveiling how an important group of signaling molecules works in the body.

The molecules, called G-protein-coupled-receptors, or GPCRs, are embedded in the membrane of cells and cause important chemical cascades when a target molecule attaches to them. That target could be anything from a hormone such as adrenaline to neurotransmitters such as dopamine.

GPCRs are different than so-called ion channels, which act as gates for charged particles to flow in and out of the cell. That's because GPCRs do not allow anything through the cell membrane.

Instead, when a target molecule -- say, adrenaline -- binds to the part of the GPCR that is outside of the cell, the shape of the GPCR inside of the cell changes slightly. It is this change in shape that begins the process of signaling inside of the cell.

In the 1970s, the existence of such target -- or ligand -- specific receptors was highly controversial. But Lefkowitz, who was studying hormones like adrenaline at the time, developed a way to use radioactive tracers to determine just what the hormones bound to in order to cause an effect in the body, such as the “fight or flight” response.

By the mid-1980s, Lefkowitz and his team -- which included Kobilka -- had identified and isolated the GPCR that adrenaline binds to, and Kobilka in particular had expanded this work to demonstrate that there is a whole family of GPCRs that are activated by different molecules.

Today, scientists believe that there are hundreds of different GPCRs in the body that react to odorants from our smells, light-sensitive molecules in our eyes, and a whole range of other peptides and transmitters that act to signal information. Though the receptors have been particularly well studied in the brain, they also play important roles in the immune system and in regulating other key body functions.

Many hundreds of laboratories are entirely focused on understanding how particular GPCRs work in the body and the brain -- a legacy directly traceable to Lefkowitz and Kobilka.

And just last year, Kobilka, who is now a professor at Stanford University, achieved a stunning breakthrough with GPCRs: He managed to capture a GPCR at the precise moment that its target molecule had arrived at the surface and a signaling cascade had begun inside the cell -- a feat the Swedish Academy, which awards the Nobel Prizes, described as “a molecular masterpiece -- the result of decades of research.”

You can read about the winners here.

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