Biology of RET receptor and its ligands: focus on the nervous system

in Endocrine-Related Cancer
Authors:
Arun Kumar Mahato Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland

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https://orcid.org/0000-0001-7541-6279
and
Mart Saarma Institute of Biotechnology, HiLIFE, University of Helsinki, Helsinki, Finland

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Correspondence should be addressed to M Saarma: mart.saarma@helsinki.fi

This paper forms part of the themed collection RET@Thirty: Three Decades of Remarkable Progress. The Guest Editors for this collection were Tom Kurzawinski, Neil McDonald and Kate Newbold.

DOI:
https://doi.org/10.1530/ERC-24-0174
Volume/Issue:
Volume 32: Issue 6
Article Type:
Review Article
Article ID:
e240174
Online Publication Date:
08 May 2025
Copyright:
© the author(s) 2025
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Abstract

The receptor tyrosine kinase RET (rearranged during transfection) is critical for many physiological processes, particularly in the development and function of the nervous system, male reproductive system and renal system. RET signaling is activated physiologically by glial cell line-derived neurotrophic factor family (GDNF) ligands or growth differentiation factor 15 (GDF15) via GDNF family receptor α (GFRα) or GDNF family receptor α-like (GFRAL) co-receptors, respectively, regulating a variety of cellular responses including cell survival, migration, differentiation, proliferation and metabolism. RET is essential for neuronal development, maintenance and axon guidance in the nervous system. RET signaling is critical for kidney and spermatogonia development and the enteric nervous system development and maintenance. Inactivating mutations in the receptor are the primary cause of Hirschsprung disease, a rare intestinal motility disorder characterized by aganglionic megacolon. This review covers the molecular mechanism of RET signaling, its role in the early stages of the nervous system and kidney development during early embryogenesis, and different diseases. It highlights the importance of RET receptors as therapeutic targets.

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© the author(s) 2025
Article ID:
e240174
Received Date:
15 Jul 2024
Rev-recd:
08 Apr 2025
Accepted Date:
24 Apr 2025
Print Publication Date:
01 Jun 2025
Online Publication Date:
08 May 2025
Keywords:
RET receptor; RET agonist; glial cell line-derived neurotrophic factor (GDNF); growth differentiation factor 15 (GDF15); GDNF family receptor α-like (GFRAL)

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