Division of labour in receptors
About 800 different G-protein coupled receptors (GPCRs) are known in the human body. A large part of that number is made up of adhesion GPCRs, which are responsible for proper brain development and inhibiting the growth of metastases and melanoma. Mutations in adhesion GPCRs, however, can lead to congenital diseases, which can cause intellectual disabilities. Despite these important functions, researchers don’t know a lot about how adhesion GPCR work so far.
The working group led by Prof. Felix Engel from the Department of Nephropathology at Universitätsklinikum Erlangen has now examined how GPR126, a receptor from the adhesion GPCR family, works. It plays an important role in cardiac development as well as in the myelination of the peripheral nervous system. The result: GPR126 works differently from what has been assumed so far.
Adhesion GPCRs have a unique molecular structure: they consist of two parts, the N-terminal (NTF), which protrudes from the cell and can interact with and receive signals from the cell’s environment or neighbouring cells, and the C-terminal (CTF), which contains seven transmembrane domains to keep it anchored in the cell membrane, and a part that protrudes into the cell interior to transfer signals.
Adhesion GPCRs are split into NTF and CTF before they anchor to the cell membrane. Up until now scientists have assumed that the split in the receptor has no impact on its function. Professor Engel and his team have now shown that each part serves a specific purpose. Using model experiments, FAU researchers have demonstrated that only the NTF – and not the CTF – plays an important role in cardiac development.
‘Our study shows that GPR126 carries out tissue-specific functions. It offers a unique example of signal transmission mechanisms of adhesion GPCRs in vertebrates,’ explains Prof. Engel. ‘This is the basic requirement for understanding the physiological and pathological functions of adhesion GPCRs and for using this knowledge in medicines in the future.’
Prof. Felix Engel
Phone: +49 (0)9131 85 25699