Notch activity is modulated by the aGPCR Latrophilin binding the DSL ligand in C. elegans

Willem Berend Post, Victoria Elisabeth Groß, Daniel Matúš, Iannis Charnay, Fabian Liessmann, Florian Seufert, Peter Hildebrand, Jens Meiler, Anette Kaiser, Torsten Schöneberg and Simone Prömel ()
Additional contact information
Willem Berend Post: Heinrich Heine University Düsseldorf
Victoria Elisabeth Groß: Heinrich Heine University Düsseldorf
Daniel Matúš: Leipzig University
Iannis Charnay: Heinrich Heine University Düsseldorf
Fabian Liessmann: Leipzig University
Florian Seufert: Leipzig University
Peter Hildebrand: Leipzig University
Jens Meiler: Leipzig University
Anette Kaiser: Leipzig University
Torsten Schöneberg: Leipzig University
Simone Prömel: Heinrich Heine University Düsseldorf

Nature Communications, 2025, vol. 16, issue 1, 1-16

Abstract: Abstract The Notch pathway is a highly conserved signaling cascade across metazoans that regulates numerous physiological processes, including cell proliferation, differentiation, and fate determination. Given its fundamental roles, the pathway is tightly regulated by diverse molecules through multiple mechanisms. Here, we identify the Adhesion GPCR latrophilin (LPHN/ADGRL) as a positive modulator of Notch signaling, which increases Notch receptor activation and the translocation of its intracellular domain into the nucleus. Physiologically, this latrophilin role is crucial for balancing the number of proliferating cells in the gonadal stem cell niche of the nematode C. elegans. In silico, in vitro, and in vivo analyses demonstrate that the C. elegans latrophilin homolog LAT-1 directly interacts with the DSL protein/Notch ligand LAG-2 on the same cell. This interaction is mediated by LAT-1’s conserved GAIN and the RBL domain. Importantly, the modulatory effect depends solely on the receptor’s N terminus and is independent of G protein signaling. Finally, we explore the implications of this fine-tuning of Notch signaling by an aGPCR.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-61730-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-61730-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-61730-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().