Cell biology: signal transmission without a signal

When we smell, taste, or see, or when adrenaline rushes through our veins, these signals are received by our cells through a specific set of receptor proteins called G protein-coupled receptors. The receptors transmit the signals into the cell interior. Biochemists at Goethe University Frankfurt and the University of Leipzig have now discovered that such receptors can also produce signals in the absence of an external stimulus: for some receptors, it is apparently sufficient if many of them move closely together on the cell surface. They have now published their findings in the journal Science.

Our bodies are made up of 100 trillion cells that communicate with each other, receiving and responding to signals from the outside world. Recipient proteins, so-called receptors, which are anchored in the cell membrane, play a central role in this communication network. There they receive signals and pass them on to the inside of the cell, where the cell's reaction is triggered.

In humans, G protein-coupled receptors (GPC receptors) represent the largest group of these receptor molecules with around 700 different types. The research of the Frankfurt and Leipzig scientists focused on a GPC receptor, which serves as a receptor for the neuropeptide Y in cells and is accordingly called the Y2 receptor. Neuropeptide Y is a messenger substance that mainly transmits signals between nerve cells, which is why Y2 receptors mainly occur in nerve cells and trigger the formation of new cell connections.

In the laboratory, the researchers - among them the biochemists Dr. Sylvia Els-Heindl and Prof. Dr. Annette G. Beck-Sickinger from the University of Leipzig - cells that each had around 300.000 Y2 receptors on their surface and grew on specially developed matrices that can be addressed with light. Each of the Y2 receptors was tagged with a small molecular 'tag'. If the scientists then used a fine laser beam to create a point of light on the cell, the Y2 receptor extensions under this spot connected to the illuminated matrix in such a way that the Y2 receptors moved closely together to form a group and formed a so-called cluster. It all happened right there and then, in a matter of seconds.

Prof. Robert Tampé from the Institute of Biochemistry at the Goethe University in Frankfurt explains: “The amazing thing about this experiment is that the clustering of the receptors triggers a signal that is similar to that of neuropeptide Y. In this way, we were able to trigger cell movements as a reaction of the cell solely through this cluster formation. With the laser spots, we were even able to control the direction in which the cell should move.” Because the light-sensitive molecules used are very small compared to the receptors, the organization of the receptors in the cell membrane can be controlled very precisely with the laser spot. "This non-invasive method is therefore particularly well suited to investigating the effects of receptor clustering in living cells," Tampé continues. "With this method, exciting scientific questions can be pursued, for example how receptors are organized in networks and how new circuits are created in the brain."

Original title of the publication in “Science”:

“Photo-induced receptor confinement drives ligand-independent GPCR signaling”, DOI: 10.1126/science.abb7657

Source: Press release University of Leipzig from February 26.02.2021th, XNUMX