NEO1

Background

The NEO1 gene is located in the 15q24.1 region of the human chromosome and encodes neogenin (NEO1), also known as immunoglobulin superfamily DCC subclass member 2 (IGDCC2), a member of the DCC receptor family within the immunoglobulin superfamily. NEO1 is a single-pass type I transmembrane glycoprotein, with a large extracellular region organized into four N-terminal immunoglobulin-like C2-type domains followed by six fibronectin type III (FNIII) repeats, a single transmembrane helix, and a substantial cytoplasmic tail of approximately 335 amino acids that contains docking sites for Src-family kinases and Rho GTPases. Its molecular weight is approximately 160 kDa and it is widely expressed during embryonic development, particularly in the developing neural tube, limb buds, and somites, with continued expression in adult tissues including the colon, liver, and central nervous system. As a multifunctional guidance receptor, NEO1 mediates both chemoattractive and chemorepulsive axon guidance: binding of netrin ligands through the FNIII domains promotes attraction and cell adhesion, while engagement of repulsive guidance molecules RGMa and RGMb through FNIII repeats 5 and 6 triggers repulsive signaling, enabling bidirectional growth cone responses. Beyond axon guidance, NEO1 functions as a receptor for bone morphogenetic proteins (BMP2, BMP4, BMP6, BMP7) and positively regulates BMP-SMAD signaling. In the liver, NEO1 binds hemojuvelin (HJV/RGMc) at the plasma membrane, and this interaction is essential for maintaining basal hepcidin expression and systemic iron homeostasis through the BMP signaling pathway. NEO1 also functions as a dependence receptor, capable of inducing apoptosis in the absence of ligand, a property shared with its paralog DCC. The cytoplasmic domain undergoes regulated intramembrane proteolysis by γ-secretase, releasing a fragment that participates in transcriptional regulation. Therefore, NEO1 is regarded as an important molecular model for studying bifunctional axon guidance mechanisms and receptor-mediated iron homeostasis. Its functional analysis provides valuable tools for understanding the molecular logic of guidance cue integration, the structural basis of ligand discrimination by FNIII domain receptors, and the regulatory networks controlling cellular iron metabolism.

Fig. 1 NET1 and RGMB can simultaneously bind NEO1 and form a ternary complex.¹

Function of NEO1 Protein: A Multifunctional Guidance Receptor Regulating Development and Iron Homeostasis

The functional spectrum of NEO1 spans axon guidance, BMP signaling, and iron homeostasis, reflecting its capacity to engage multiple structurally distinct ligand families:

• Bifunctional axon guidance: NEO1 mediates both chemoattractive and chemorepulsive responses in developing axons through differential ligand engagement. Netrin-1 binding to NEO1 activates attractive signaling cascades involving Src-family kinases and Rho GTPases that promote growth cone extension and cell adhesion. In contrast, binding of RGMa or RGMb to the FNIII repeats 5 and 6 triggers repulsive signaling that redirects axonal trajectories. This bidirectional capacity distinguishes NEO1 from other guidance receptors and enables context-dependent navigation during neural circuit assembly.
• BMP signaling and developmental regulation: NEO1 functions as a co-receptor for bone morphogenetic proteins including BMP2, BMP4, BMP6, and BMP7, positively regulating the BMP-SMAD signaling pathway. Through this mechanism, NEO1 contributes to neural tube closure, chondrogenesis, myogenesis, and mammary gland morphogenesis during embryonic and postnatal development.
• Iron homeostasis and hemojuvelin interaction: NEO1 binds hemojuvelin (HJV/RGMc) at the hepatocyte plasma membrane through its FNIII repeats, forming a complex that facilitates BMP receptor activation and subsequent hepcidin transcription via SMAD signaling. This NEO1-HJV-BMP receptor axis establishes the basal level of hepcidin expression, the master regulator of systemic iron homeostasis. Upon HJV binding, NEO1 undergoes γ-secretase-mediated intramembrane cleavage, releasing its cytoplasmic domain, a processing event required for full hepcidin induction.
• Dependence receptor function and intracellular signaling: In the absence of ligand, NEO1 can initiate apoptotic signaling through caspase-mediated cleavage of its cytoplasmic domain, exposing a pro-apoptotic fragment — a property characteristic of dependence receptors. The cytoplasmic tail also interacts with multiple downstream effectors including Src-family kinases and Rho-family GTPases, linking extracellular guidance cues to cytoskeletal reorganization and transcriptional responses. Elucidating how these diverse signaling outputs are integrated at the molecular level provides insights into the regulatory principles governing multifunctional receptor biology.

NEO1 Membrane Protein Product

Creative Biolabs offers a comprehensive series of high-quality NEO1 membrane protein products designed to support structural and functional investigations of guidance receptor signaling and ligand-receptor interactions. Built upon the independently developed MemDX™ recombinant membrane protein technology platform, NEO1 proteins can be prepared through multiple expression systems, including virus-like particles (VLP) and in vitro prokaryotic expression systems, among others. These rigorously characterized protein products, which include MemDX™ recombinant human NEO1 membrane protein (as virus-like particles) and human NEO1 proteins derived from diverse expression systems, are suitable for ELISA, antibody screening and identification, ligand-receptor binding experiments, and functional research, equipping investigators with dependable reagents for analyzing NEO1-mediated axon guidance mechanisms and iron regulatory signaling.

NEO1 Protein Product

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NEO1 Stable Cell Line Product

Constructing a robust cell model is crucial for investigating NEO1 function in guidance receptor signaling and iron homeostasis. As a plasma membrane receptor that differentially responds to netrins and RGMs to produce opposing guidance outputs, the expression level, surface distribution, and ligand-binding properties of NEO1 directly determine cellular responses to guidance cues and BMP signals. Alterations in NEO1 expression or changes in its FNIII domain conformation may lead to significant shifts in signaling output. Creative Biolabs offers customized NEO1 membrane protein stable transfection cell models, covering wild-type and various functionally characterized forms. These models stably express the target protein on the plasma membrane, and are suitable for studies on netrin and RGM ligand binding, BMP signaling pathway activation, growth cone collapse and extension assays, and quantitative assessment of hepcidin regulatory responses, providing a reliable and reproducible platform for exploring the molecular mechanism, structure-function relationship, and regulatory role of NEO1 in development and iron metabolism. Our technology ensures correct protein localization and plasma membrane integrity, facilitating your research.

NEO1 Stable Cell Line Product

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NEO1 Recombinant Antibody Product

Creative Biolabs offers highly specific recombinant antibodies targeting NEO1, produced using advanced recombinant antibody technology. Compared to traditional antibodies, these recombinant antibodies demonstrate superior performance in terms of specificity, sensitivity, and batch-to-batch consistency. They can also be modified and labeled in various ways. Our NEO1 recombinant antibodies support a wide range of applications, including Western Blot, ELISA, flow cytometry, immunofluorescence, immunocytochemistry, immunohistochemistry, and immunoprecipitation, and can be used to detect differences in NEO1 expression levels in developing and adult tissues, analyze its plasma membrane distribution and FNIII domain accessibility, and conduct related research such as ligand-receptor binding analysis and BMP signaling pathway investigation. These antibodies provide reliable detection tools for the structural analysis, functional study of NEO1, and the investigation of its role in axon guidance and iron homeostasis.

NEO1 Recombinant Antibody Product

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Product Features

• Multiple expression platforms: Recombinant proteins can be produced through several expression systems (encompassing virus-like particles and both prokaryotic and eukaryotic hosts), addressing the requirements of diverse experimental settings.
• Broad experimental compatibility: The products are suitable for use in ELISA, antibody screening, binding assays, Western Blot, immunofluorescence, immunohistochemistry, and related applications.
• Consistent quality across batches: Strict quality control measures maintain product uniformity between batches, ensuring experimental results remain reproducible and dependable.
• Tailored customization services: Personalized services are available for specific protein forms, labeling approaches, or preferred expression platforms.

Custom NEO1 Membrane Protein and Antibody Discovery Services

In addition to the standard products, Creative Biolabs also offers professional customized services for NEO1. NEO1 is a large multi-domain transmembrane receptor with four immunoglobulin-like domains and six fibronectin type III repeats, and its ligand specificity for netrins, RGMs, and BMPs is determined by distinct regions within the extracellular domain. These structural features present specific requirements in aspects such as membrane protein expression, antigen design, and functional characterization. Leveraging our technology platform, we can assist you in completing the following customized projects:

• Customized production of guidance receptor membrane proteins: Tailored expression (using multiple expression systems), purification, and characterization for full-length NEO1 and its individual extracellular domains including the FNIII repeat region and the RGM-binding FNIII 5–6 module.
• Customized antibody development: From antigen design to antibody engineering (monoclonal, polyclonal, recombinant antibodies), supporting detection of distinct NEO1 extracellular domains or conformation-specific epitopes.
• Construction of stable cell models: Generate stable cell models expressing wild-type or domain-modified NEO1, suitable for ligand binding and signaling studies.
• Development of functional detection systems: Design and execute experimental protocols such as netrin and RGM binding assays, BMP signaling pathway measurements, and quantitative assessment of NEO1-dependent hepcidin regulation.

Frequently Asked Questions (FAQ)

1. What is the main function of the NEO1 protein?

   NEO1, also known as neogenin, functions as a multifunctional cell surface receptor that mediates both chemoattractive and chemorepulsive axon guidance during neural development. It binds netrin ligands to promote attraction and cell adhesion, while engagement of RGMa and RGMb through its FNIII repeats 5 and 6 triggers repulsive responses, enabling bidirectional growth cone navigation. Beyond axon guidance, NEO1 serves as a BMP co-receptor and is essential for iron homeostasis through its interaction with hemojuvelin in hepatocytes, which drives hepcidin expression via the BMP-SMAD pathway. NEO1 also functions as a dependence receptor capable of initiating apoptosis in the absence of ligand.

2. Why is NEO1 an important research target?

   NEO1 possesses a unique capacity to integrate multiple structurally distinct ligand inputs — netrins, RGMs, and BMPs — and translate them into diverse cellular responses including attraction, repulsion, differentiation, and apoptosis. Investigating NEO1 provides insights into the molecular mechanisms of bifunctional axon guidance, the structural basis of FNIII-mediated ligand discrimination, and the γ-secretase-dependent signaling pathways controlling iron homeostasis. The receptor's modular domain architecture, dependence receptor properties, and essential roles in both development and adult physiology make it a valuable model for studying how a single receptor coordinates pleiotropic biological functions.

3. Is the NEO1 product of Creative Biolabs suitable for clinical applications?

   Not applicable. All NEO1 products and services provided by Creative Biolabs are for research purposes only and cannot be used for any clinical diagnosis, prevention, treatment or cure of any disease.

4. What types of NEO1 products does Creative Biolabs offer?

   We offer a variety of product types, including recombinant NEO1 membrane proteins, stable cell models expressing NEO1, high-quality recombinant NEO1 antibodies, as well as comprehensive customized services.