Endocrine Abstracts

The spatial organisation of receptors at the macro and micro-scale is critical for the tight regulation of cell signalling, including signalling activated by the superfamily of G protein-coupled receptors (GPCRs). To study these processes, a range of imaging techniques have been employed including an increasing application of super-resolution microscopy to image receptor activity beyond the diffraction limit of light. In this session, I will highlight the experimental and imaging approaches we have used to study GPCR signalling at the macro-level, through the identification of divergent endosomal organisation and signalling from a novel endosomal compartment we have termed very early endosomes (VEEs). Furthermore, our studies at the ‘micro-level’ of GPCR signalling, via the application of super-resolution/single-molecule imaging, has revealed how the organisation of GPCRs in functionally asymmetric oligomeric complexes, impacts both signal sensitivity and diversity. These imaging tools have contributed to our evolved understanding of GPCR signalling, providing models to understand how cells can achieve highly specific diverse downstream responses in dynamic extracellular environments, offer new interpretations of faulty GPCR activity in disease and provide novel therapeutic strategies to target GPCR signalling.