Adhesion GPCRs in the neural and vascular systems: from complex structures to cellular functions

Year of award: 2016

Grantholders

  • Prof Elena Seiradake

    University of Oxford

Project summary

A family of proteins known as the adhesion G-protein-coupled receptors (adhesion GPCRs) are produced by cells in the brain and blood vessels. They have been implicated in a number of severe human disorders including neurodevelopmental disorders, drug addiction and cancer. They are present on the cell membrane and contain a large extracellular region, through which adhesion GPCRs interact with other diverse proteins. The mechanics of how adhesion GPCR interact and function are poorly understood, hampering progress in understanding their biological roles and mode of action. My previous work has shown for the first time that up to four copies of the adhesion GPCR latrophilin assemble together when bound to two unrelated proteins (FLRT and Unc5).

I now aim to understand how adhesion GPCRs regulate the development of brain tissue and blood vessels. My goals are to reveal further details on the structures and functions of latrophilin assemblies with their partners, find out how these direct brain cortex development, reveal how additional brain molecules control latrophilin functions, and understand how latrophilin and other adhesion GPCRs function in blood vessels. 

The results will reveal fundamental new insights into the roles of adhesion GPCRs in tissue formation and disease.