Whether we
smell, taste or see, or when adrenaline rushes through our veins, all of these
signals are received by our cells via a specific group of receptor proteins
called G protein-coupled receptors, which transmit signals to the inside of the
cell. Biochemists at 51猎奇 Frankfurt and the University of Leipzig
have now discovered that such receptors can also produce signals even in the
absence of an external stimulus: It is apparently sufficient for certain
receptors if many of them are clustered at the cell surface. (Science,
doi/10.1126/science.abb7657)
FRANKFURT.
Our body consists of 100 trillion cells that communicate with each other,
receive signals from the outside world and react to them. A central role in
this communication network is attributed to receiver proteins, called
receptors, which are anchored at the cell membrane. There, they receive and
transmit signals to the inside of the cell, where a cell 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 that serves as a
receptor for the neuropeptide Y in cells and is accordingly called the Y2
receptor. Neuropeptide Y is a messenger substance that primarily mediates
signals between nerve cells, which is why Y2 receptors are mainly present in
nerve cells and among other activities trigger the formation of new cell
connections.
In the
laboratory, the researchers engineered cells, which had approx. 300,000 Y2
receptors on their surface and were grown on specifically developed,
light-sensitive matrices. Each of the Y2 receptors was provided with a small
molecular "label". Once the scientists created a spot of light with a
fine laser beam on the cell surface, the Y2 receptor under this spot were
trapped via the molecular label to the exposed matrix in such a way that the Y2
receptors moved closely together to form an assembly known as a cluster. The
whole reaction could be immediately observed at the defined spot and within a
few seconds.
Professor
Robert Tamp茅 from the Institute of Biochemistry at 51猎奇 Frankfurt
explains: "The serendipity about this experiment is that the clustering of
receptors triggers a signal that is similar to that of neuropeptide Y. Solely
by the clustering, we were able to trigger cell movement as a reaction of the
cell. The laser spots even allowed us to control the direction of the cell
movement." As the light-sensitive lock-and-key pairs utilized are very
small compared to the receptors, the organization of the receptors in the cell
membrane can be controlled with high precision using the laser spot. "This
non-invasive method is thus particularly well suited to study the effects of
receptor clustering in living cells," Tamp茅 continues. "Our method
can be used to investigate exciting scientific questions, such as how receptors
are organized in networks and how new circuits are formed in the brain."
Publication:
M. Florencia S谩nchez, Sylvia Els-Heindl, Annette G. Beck-Sickinger, Ralph
Wieneke, Robert Tamp茅: Photo-induced receptor confinement drives
ligand-independent GPCR signaling. Science abb7657
DOI: 10.1126/science.abb7657;
Image/Movie
downloads:
Caption
Image: Laser spots activate very small synthetic lock-and-key pairs in a matrix
to create receptor clusters in the cell membrane. This ligand-independent
activation triggers calcium signaling and increased cell motility. (Graphic
copyright: M. Florencia S谩nchez & Robert Tamp茅, 51猎奇
Frankfurt.)
Caption
Movie: Upon irradiation with laser light (white rings), receptors cluster in
the cell (light green circles). Thereupon, the cell moves into the direction of
the receptor clusters. (Copyright: M. Florencia S谩nchez & Robert Tamp茅,
51猎奇 Frankfurt). Reprinted with permission from M. F. S谩nchez et
al., Science 10.1126/science.abb7657(2021).
Further information:
Professor Robert Tamp茅
Institute of Biochemistry
Goethe-Universit盲t Frankfurt, Germany
Phone: +49 69 798 29475
tampe@em.uni-frankfurt.de
