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GFRAL identified as receptor for GDF15 using cell microarray technology
A paper, recently published in the journal Nature Medicine, describes the identification of the cognate receptor for a ligand that correlates with weight loss, and marks a major milestone towards development of a pharmacotherapy for obesity. The receptor identification work was undertaken by Retrogenix on behalf of the study sponsors, Janssen Research & Development.
Although a role for the GDF15 ligand in weight loss had previously been identified, the group demonstrated a specific link between pharmacologically administered GDF15 and decreased energy intake, underscoring the great potential for GDF15 as a therapy. In order to understand the mechanism of action of GDF15, the next step was to identify its specific receptor.
Recombinant Fc-GDF15 was used in an unbiased screen of 4,493 plasma membrane proteins expressed in the Retrogenix cell microarrays. This resulted in the identification of GFRAL as a specific binding partner for GDF15.
Further characterisation by Janssen confirmed the GFRAL receptor as a node in this newly identified body-weight signalling pathway. The study also revealed that GFRAL signalling through GDF15 is dependent on the co-receptor RET.
This high impact research highlights the advantage of rapid and reliable receptor identification in driving progress in the development of novel therapies. To view the study abstract and full text options please visit the Nature Medicine website.
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