ArticleFEBS letters2025
Glu592 of the axon guidance receptor ROBO3 mediates a pH-dependent interaction with NELL2 ligand.
Article in FEBS letters, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- Deciphering the functions of NELL2 in tumorigenesis and beyond.Frontiers in immunology · 2026Review
- The Slit-Robo signalling pathway in nervous system development: a comparative perspective from vertebrates and invertebrates.Open biology · 2025Review
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Authors and funding
5 authors.
Funding
Abstract
There are only a few studies on the function of neuronal axon guidance molecules during low brain pH conditions. We previously reported that roundabout (ROBO) 2, a receptor for the axon guidance molecule SLIT, can bind to the neural epidermal growth factor-like-like (NELL) ligands in acidic conditions by conformational change of its ectodomain. Here, we show that the ROBO3 receptor also exhibits a pH-dependent increase in binding to the NELL2 ligand. We found that the Glu592 residue of ROBO3 at the binding interface between NELL2 and ROBO3 is a pH sensor and that the formation of a new hydrogen bonding network, due to protonation of the Glu592, leads to increased binding in acidic conditions. These results suggest that NELL2-ROBO3 signaling could be regulated by extracellular pH.
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