DCC netrin 1 receptor | Elisa - Clia - Antibody - Protein

Background

The Deleted in Colorectal Carcinoma (DCC) gene encodes a transmembrane receptor for netrin-1, a crucial guidance cue for axonal growth and cell migration. Originally identified due to its deletion in colorectal cancer cells, DCC plays significant roles in neural development, particularly in axon guidance, neuronal migration, and cell survival. Netrins are a family of laminin-related proteins that guide axons during neural development by binding to receptors like DCC. The interaction between netrin-1 and DCC is pivotal for directing axons to their correct targets, ensuring proper neural network formation.

Protein Structure

The DCC protein is a single-pass transmembrane receptor composed of several distinct domains:

1. Extracellular Domain: The extracellular portion of DCC includes four immunoglobulin-like (Ig) domains followed by six fibronectin type III (FNIII) domains. The Ig domains are critical for binding to netrin-1, while the FNIII domains are involved in protein-protein interactions and signal transduction.
2. Transmembrane Domain: This single transmembrane segment anchors DCC to the cell membrane, positioning the extracellular domain for netrin-1 binding and the intracellular domain for signal transduction.
3. Intracellular Domain: The intracellular region of DCC contains several motifs important for signaling, including P1 and P2 domains which interact with cytoplasmic proteins involved in axon guidance and cell survival pathways. This region mediates interactions with other intracellular signaling molecules and adaptor proteins, facilitating downstream signaling cascades.

Classification and Subtypes

DCC belongs to the immunoglobulin superfamily (IgSF) of cell adhesion molecules. While DCC itself does not have subtypes, it functions alongside other netrin receptors such as:

• Neogenin: A receptor similar to DCC, also binding netrin-1 but with additional roles in cell adhesion and tissue morphogenesis.
• UNC5H: Receptors that can mediate both attraction and repulsion in response to netrin-1, depending on the cellular context.

Function and Biological Significance

DCC serves multiple roles in the nervous system and beyond:

1. Axon Guidance: DCC is essential for the proper navigation of axons during neural development. By binding netrin-1, DCC directs the growth cones of developing axons towards regions of high netrin-1 concentration, ensuring that axons reach their appropriate targets.
2. Cell Migration: DCC also influences the migration of neurons and other cell types during embryonic development. This process is crucial for the formation of layered structures in the brain and the establishment of neural circuits.
3. Cell Survival and Apoptosis: In the absence of netrin-1, DCC can trigger apoptosis, a mechanism that helps eliminate misplaced or excess neurons during development. Conversely, netrin-1 binding can promote cell survival, highlighting the dual role of DCC in cell fate determination.
4. Tumor Suppression: Given its name, DCC is recognized for its tumor suppressor functions. Loss or mutation of DCC is associated with various cancers, particularly colorectal cancer, where its absence can lead to uncontrolled cell growth and tumor development.

Clinical Issues

Dysfunction or altered expression of DCC has been linked to several pathological conditions:

1. Cancer: The most well-studied association is with colorectal cancer, where loss of DCC expression is a common event. DCC's role as a tumor suppressor is crucial in maintaining normal cellular growth and preventing malignancy.
2. Neurodevelopmental Disorders: Mutations in DCC or aberrant netrin-1 signaling can result in congenital mirror movements, a condition where voluntary movements on one side of the body are mirrored involuntarily on the other side. This highlights DCC's role in axonal guidance and the establishment of neural circuits.
3. Spinal Cord Injuries: Research indicates that DCC and netrin-1 signaling are involved in the regeneration and repair processes following spinal cord injuries, offering potential therapeutic targets for enhancing neural repair and recovery.

Summary

The DCC (Deleted in Colorectal Carcinoma) receptor is a critical protein involved in neural development, particularly in axon guidance, cell migration, and cell survival. Structurally, DCC is characterized by an extracellular region with Ig and FNIII domains, a single transmembrane segment, and an intracellular domain crucial for signaling. As a receptor for netrin-1, DCC directs axonal growth and influences cell migration, playing a significant role in the formation and maintenance of neural networks. Clinically, DCC is recognized as a tumor suppressor, with its loss or mutation being implicated in colorectal cancer and other malignancies. Additionally, DCC's involvement in neurodevelopmental disorders and potential in spinal cord injury repair underscores its broader biological significance. Understanding the molecular mechanisms and pathways involving DCC is essential for developing targeted therapies for cancer, neurodevelopmental disorders, and neural injuries.