Dr Leonid Nikitenko L.Nikitenko@hull.ac.uk
Lecturer in Biomedical Sciences
The characterisation of G-protein coupled receptor CLR in human endothelial cells
People Involved
Project Description
Calcitonin receptor-like receptor (CLR) is a key G-protein-coupled receptor (GPCR) mediating the effects of three peptide agonists - adrenomedullin (AM), calcitonin gene-related peptide (CGRP) and intermedin (IMD/AM-2) in ectopic expression studies. Animal models revealed critical roles for these molecules in cardiovascular disease, migraine, lymphoedema and cancer. However, CLR properties in human tissues, where it is predominantly expressed in endothelial cells (EC), are poorly understood/characterised, limiting avenues for translational research. Proposed fundamental research project will address this knowledge gap by analysing CLR role in mediating effects of its putative agonists in primary EC from human blood and lymphatic vessels.
Recently my group has discovered that AM, CGRP and IMD/AM-2 play a role in human lymphatic EC (LEC) by promoting proliferation and p44/42 MAPK phosphorylation, but inducing very distinct transcriptional responses and CLR internalisation profiles.
The key aim of the proposed scholarship project is to further compare and contrast molecular mechanisms underlying the effects of three putative CLR agonists in primary human EC, including:
1. Agonist-induced activation of signalling pathways by using qRT-PCR and immunoblotting.
2. Agonist-induced CLR internalisation and receptor desensitisation by using immunoblotting and immunofluorescence.
3. Confirmation that these effects are CLR-mediated by using antagonists and RNAi methods.
| Status | Project Complete |
|---|---|
| Value | £1,600.00 |
| Project Dates | Jun 10, 2019 - Aug 2, 2019 |
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