Gfral
Function
Brainstem-restricted receptor for GDF15 hormone, which triggers an aversive response, characterized by nausea, vomiting, and/or loss of appetite in response to various stresses (PubMed:28846097, PubMed:28846098, PubMed:28846099, PubMed:28953886, PubMed:31152154, PubMed:31928886, PubMed:32723474, PubMed:33593916, PubMed:35202387, PubMed:36630958, PubMed:37380764). The aversive response is both required to reduce continuing exposure to those stresses at the time of exposure and to promote avoidance behavior in the future (PubMed:28846097, PubMed:28846098, PubMed:28846099, PubMed:28953886, PubMed:31928886, PubMed:32723474, PubMed:33593916, PubMed:35202387, PubMed:36630958). The GDF15-GFRAL aversive response is triggered by stresses, such as anticancer drugs (camptothecin or cisplatin), cancers or drugs such as metformin (PubMed:31875646, PubMed:31928886, PubMed:32661391, PubMed:32723474). Upon interaction with its ligand, GDF15, mediates the GDF15-induced autophosphorylation and activation of the RET tyrosine kinase receptor, leading to activation of MAPK- and AKT- signaling pathways (PubMed:28846098, PubMed:28846099, PubMed:32723474, PubMed:33593916). Ligand-binding activates GFRAL-expressing neurons localized in the area postrema and nucleus tractus solitarius of the brainstem (PubMed:28846098, PubMed:28846099, PubMed:31152154, PubMed:32723474). The GDF15-GFRAL signal induces expression of genes involved in metabolism, such as lipid metabolism in adipose tissues (PubMed:32661391).
Post-translational modifications
Cleaved and inactivated by MMP14, inhibiting the GDF15-GFRAL aversive response.
Sequence Similarities
Belongs to the GDNFR family.
Tissue Specificity
Expressed in the brainstem, restricted to cells in the area postrema and the immediately adjacent region of the nucleus tractus solitarius.
Cellular localization
- Cell membrane
- Single-pass membrane protein
- Extracellular side
Alternative names
Gral, Gfral, GDNF family receptor alpha-like