NEO1 - neogenin 1 | Elisa - Clia - Antibody - Protein

Background

Neogenin 1 (NEO1) is a multifunctional transmembrane receptor protein encoded by the NEO1 gene, located on chromosome 15q22.31. It belongs to the immunoglobulin superfamily and is closely related to the Netrin receptors, particularly the Deleted in Colorectal Cancer (DCC) protein. Neogenin 1 plays a pivotal role in a variety of biological processes, including axon guidance, cell migration, apoptosis, and tissue development. Originally identified in neural tissues, NEO1 is now known to be expressed in multiple tissues, indicating its broad biological significance. The receptor is involved in crucial signaling pathways that dictate cell fate and organization during embryonic development and in the adult organism.

Protein Structure

The Neogenin 1 protein consists of several key structural features:

1. Extracellular Domain:

• Immunoglobulin-like Domains: NEO1 contains four immunoglobulin-like (Ig) domains, which are essential for its role in cell adhesion and interaction with ligands such as Netrins and Repulsive Guidance Molecules (RGMs).
• Fibronectin Type III Domains: Following the Ig domains, there are six fibronectin type III (FNIII) domains, which contribute to protein-protein interactions and provide structural stability.

1. Transmembrane Domain: This single-pass transmembrane region anchors NEO1 in the cell membrane, facilitating its role as a receptor that can transmit extracellular signals to the intracellular environment.
2. Intracellular Domain:

• The cytoplasmic portion of NEO1 contains multiple phosphorylation sites that allow interaction with intracellular signaling proteins, including members of the Src family kinases and Rho GTPases. These interactions are crucial for translating extracellular cues into cellular responses.

Classification and Subtypes

NEO1 is classified as a member of the immunoglobulin superfamily and is closely related to the DCC protein family. Within its classification, NEO1 is distinguished by its ability to interact with both attractive and repulsive guidance cues, a unique feature compared to other family members.

• Netrin Receptors: Like DCC, NEO1 can bind Netrins, which are bifunctional molecules involved in axon guidance.
• RGMs: NEO1 also binds RGMs, which are involved in neuronal patterning and bone morphogenesis.

Function and Biological Significance

Neogenin 1 is implicated in several critical biological functions:

1. Axon Guidance and Neural Development: NEO1 plays a central role in axon guidance by responding to Netrins, guiding axonal growth cones during neural development. It helps in the formation of neural networks by mediating attractive and repulsive signaling.
2. Cell Migration and Adhesion: Through its interaction with RGMs, NEO1 regulates cell migration and adhesion, essential for tissue formation and repair.
3. Apoptosis and Cell Survival: NEO1 is involved in apoptotic signaling pathways. It can promote apoptosis in response to certain signals, thereby contributing to tissue homeostasis and development.
4. Tissue Development and Morphogenesis: Beyond the nervous system, NEO1 is involved in the morphogenesis of various tissues, including muscle and bone, by interacting with growth factors and extracellular matrix components.
5. Tumor Suppression and Cancer: Similar to DCC, NEO1 is considered a dependence receptor, meaning it can induce apoptosis in the absence of its ligand, which might suppress tumor formation. However, in certain contexts, its expression has been linked to cancer progression, indicating a complex role in oncogenesis.

Clinical Issues

The diverse functions of NEO1 implicate it in several clinical conditions:

1. Cancer: Alterations in NEO1 expression have been observed in various cancers. While it can act as a tumor suppressor by inducing apoptosis, some studies suggest that in certain cancers, such as glioblastoma, NEO1 might contribute to tumor cell survival and invasion.
2. Neurodevelopmental Disorders: Given its critical role in neural development, mutations or dysregulation of NEO1 can potentially contribute to neurodevelopmental disorders, though specific links require further research.
3. Bone and Muscle Disorders: NEO1's involvement in bone morphogenesis and muscle development suggests that its dysfunction could lead to developmental anomalies or degenerative conditions in these tissues.

Summary

Neogenin 1 (NEO1) is a versatile receptor protein that plays essential roles in neural development, tissue morphogenesis, and cellular homeostasis. Structurally, it features multiple Ig-like and FNIII domains, a transmembrane region, and an intracellular domain with signaling capacity. Functionally, NEO1 mediates axon guidance, cell migration, apoptosis, and tissue development by interacting with Netrins and RGMs. Clinically, NEO1's expression and function are implicated in cancer, neurodevelopmental disorders, and potentially bone and muscle diseases. Understanding NEO1's diverse roles in cellular processes and disease states highlights its significance in both basic biology and clinical research.