September 2021

Dr. GPCR Virtual Cafe

Dr. GPCR Ecosystem  -  Virtual Cafe  -  September 2021
 

        


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Dr. GPCR Ecosystem 

      

Adhesion GPCRs: Cis and trans-signaling shape communication in cell polarity and division

     

Abstract

 

Adhesion G protein-coupled receptors (aGPCRs) are an unusual class of GPCRs with a puzzling diversity of functions in health and disease. They set themselves apart from other GPCRs by their structural and functional diversity and their unique features such as extraordinarily long extracellular N termini comprising various domains. With these special N termini, Adhesion GPCRs display a broad repertoire of ways to mediate cell-cell communication. To do so, Adhesion GPCRs mediate G protein signals into cells (cis signaling) as well as a function completely independent of seven transmembrane domains and C terminus (trans-signaling).

To investigate how Adhesion GPCRs shape cellular communication by this dual mode of signaling, we study Latrophilins as prototypic Adhesion GPCRs, which belong to the oldest members of the receptor class. Using the roundworm Caenorhabditis elegans as a model, we found that the Latrophilin homolog LAT-1 signals via a Gs protein pathway upon activation by a tethered agonistic sequence to coordinate anterior-posterior tissue polarity in the developing embryo. We were able to show that the cis mode coveys a non-polar signal to polarize a cell. Interestingly, while cell polarity is mediated by a classical G protein cascade, LAT-1 also controls cell proliferation solely through its N terminus. This peculiar trans mode is a non-cell-autonomous signal cross-talking with the Notch cascade on the cell membrane.

Both modes seem to be a common feature for several Adhesion GPCR. Their ability to mediate two distinct signals in different biological contexts constitutes a novel signaling principle of this intriguing GPCR class and might be a key in mediating cellular changes.

   
  

About Dr. Simone Prömel


Dr. Simone Prömel is currently a professor of cell biology at the Heinrich Heine University Düsseldorf, Germany. Being a biochemist by training, she completed her Ph.D. at the Institute of Biochemistry at the University of Oxford, UK. During this time, she discovered her love for Adhesion GPCRs and started delineating the molecular mechanisms of the Adhesion GPCR Latrophilin-1.

These extraordinary receptors, about which there was not much known other than that they are huge and somehow play important roles in health and disease, fascinated her so much that she continued working on them when she started her own lab at Leipzig University. There she focused on the different modes of action of Adhesion GPCRs and found that they do not only mediate classical G protein signals into cells but can also communicate solely via their N termini.

Today, she and her team are working on the questions of how Adhesion GPCRs integrate the different signals on a molecular level and how these are translated into physiological functions in various model organisms. Together with Ines Liebscher, Simone is leading an EU-funded COST Network on Adhesion GPCRs: CA18240 Adher´n Rise.
        

 

Dr. Simone Prömel on the web

        

      

       
 

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