ArticleThe Journal of biological chemistry2019
Robo2 contains a cryptic binding site for neural EGFL-like (NELL) protein 1/2.
Article in The Journal of biological chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- Evolution of NELL binding by dual-ligand-responsive axon guidance receptor Robo.bioRxiv : the preprint server for biology · 2026Article
- Deciphering the functions of NELL2 in tumorigenesis and beyond.Frontiers in immunology · 2026Review
- Tracing the Genetic Heritage of the Kirgiz People: Dual-Wave Admixture and Ancestry-Biased Adaptation.Molecular biology and evolution · 2025Article
- The Slit-Robo signalling pathway in nervous system development: a comparative perspective from vertebrates and invertebrates.Open biology · 2025Review
- Glu592 of the axon guidance receptor ROBO3 mediates a pH-dependent interaction with NELL2 ligand.FEBS letters · 2025Article
- Role of NEL‑like molecule‑1 in osteogenesis/chondrogenesis (Review).International journal of molecular medicine · 2025Review
- Role of Csdc2 in Regulating Secondary Hair Follicle Growth in Cashmere Goats.International journal of molecular sciences · 2024Article
- Function of cell adhesion molecules in differentiation of ray sensory neurons in C. elegans.G3 (Bethesda, Md.) · 2023Article
- CNTNAP4 signaling regulates osteosarcoma disease progression.NPJ precision oncology · 2023Article
- Structure and evolution of neuronal wiring receptors and ligands.Developmental dynamics : an official publication of the American Association of Anatomists · 2023Review
- Role of the SLIT-ROBO signaling pathway in renal pathophysiology and various renal diseases.Frontiers in physiology · 2023Review
- Transcriptional Regulatory Role of NELL2 in Preproenkephalin Gene Expression.Molecules and cells · 2022Article
- Weighted Single-Step Genome-Wide Association Study Uncovers Known and Novel Candidate Genomic Regions for Milk Production Traits and Somatic Cell Score in Valle del Belice Dairy Sheep.Animals : an open access journal from MDPI · 2022Article
- NELL-1 in Genome-Wide Association Studies across Human Diseases.The American journal of pathology · 2022Review
- Positioning-dependent bidirectional NELL2 signaling in the brain.Frontiers in endocrinology · 2022Article
- Role of Slit/Robo Signaling pathway in Bone Metabolism.International journal of biological sciences · 2022Review
- Anoctamin 5 promotes osteosarcoma development by increasing degradation of Nel-like proteins 1 and 2.Aging · 2021Article
- Robo2 Receptor Gates the Anatomical Divergence of Neurons Derived From a Common Precursor Origin.Frontiers in cell and developmental biology · 2021Article
- Roles of Slit Ligands and Their Roundabout (Robo) Family of Receptors in Bone Remodeling.Advances in experimental medicine and biology · 2021Review
- Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The signaling pathways that are mediated by Slit ligands and their Roundabout (Robo) family of receptors play multifunctional roles in the development of the nervous system and other organs. A recent study identified neural epidermal growth factor-like (NEL)-like 2 (NELL2) as a novel ligand for Robo3. In this study, we carried out a comprehensive analysis of the interaction between NELL1 and the Robo family of receptors and demonstrated that Robo2 contains a cryptic binding site for both NELL1 and NELL2. NELL1/2 binds to the first fibronectin type III (FNIII) domain of Robo2 but not to intact Robo2. Mutation analysis revealed that several amino acids within the first FNIII domain are critical for NELL1 binding to Robo2 but not to Robo1. The Robo2 deletion mutants without the fourth immunoglobulin domain and single amino acid substitution mutants that can influence the architecture of the ectodomain facilitated binding to NELL1/2. Acidic conditions increased the binding affinity of Robo2 for NELL1. These results suggest that Robo2 functions as a receptor for NELL1/2, particularly under circumstances where Robo2 undergoes proteolytic digestion. If this is not the case, conformational changes of the ectodomain of Robo2 may unmask the binding site for NELL1/2.
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