Locking without a lock
Scientists in Kiel discover new mechanism for cell communication
Cells within an organism communicate with each other in order to control various processes like cell growth or repair mechanisms. During this communication between cells, a ligand normally binds to a receptor which is located in the cell membrane. Scientists from the Faculty of Medicine at Kiel University, from the Institute for Anatomy (PD Dr Kirsten Hattermann, Professor Dr Rolf Mentlein) and from the Department of Neurosurgery (Prof. Dr Dr Janka Held-Feindt) have now succeeded in discovering a completely new effect mechanism of cell communication. The results of their studies were recently published in the journal eLIFE.
If cells wish to communicate with one another, first a ligand from one cell must bind to a matching receptor on the surface of another cell. Like a key that only opens a certain lock, a ligand can only bind to its matching receptor. When this happens, signals are sent to the centre of the cell. "We were able to find a completely new effect mechanism in which the signals are sent without a receptor, so only with a ligand", explains PD Dr Kirsten Hattermann from the Institute for Anatomy, one of the main authors of the study.
In this joint project between the Institute for Anatomy and the Department of Neurosurgery, the scientists were able to show that although brain tumour cells formed large amounts of the ligands CXCL16 and CX3CL1, which were embedded in the cell membrane, they didn't have any matching receptors. Instead, part of the ligand that is outside of the cell is split off in these cells. This soluble ligand binds to its equivalent in the membrane, which itself acts as a receptor and passes the information into the cell. These chains of signals which have then been activated promote cell growth and make the cells resistant to treatment. The scientists in Kiel presume that this newly described mechanism helps regulate the fine-tuning in the communication between cells and have termed it 'inverse signaling'.
Transmembrane chemokines act as receptors in a novel mechanism termed inverse signaling. Kirsten Hattermann, Henrike Gebhardt, Sebastian Krossa, Andreas Ludwig, Ralph Lucius, Janka Held-Feindt, Rolf Mentlein. eLife 2016;5:e10820
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Whereas during classic cell communication, a receptor (blue) binds to a ligand (red) according to the lock-and-key principle, in the newly discovered communication path an enzyme releases a soluble form of the membrane-bound ligand, which then binds to its own equivalent.
Image/Copyright: Hattermann/Institute for Anatomy, Kiel University
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PD Dr Kirsten Hattermann
Institute for Anatomy
Tel.: +49 (0)431 880-3085
Prof. Dr Dr Janka Held-Feindt
The Department of Neurosurgery
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