ADGRE - Adhesion G protein-coupled receptor E | Elisa - Clia - Antibody - Protein

Background

Adhesion G protein-coupled receptor E (ADGRE), formerly known as EMR4, is a member of the adhesion G protein-coupled receptor (GPCR) family, characterized by its unique structure containing a large extracellular domain involved in cell-cell and cell-matrix interactions. ADGRE receptors play diverse roles in various physiological processes, including immune response regulation, inflammation, and tissue homeostasis. They mediate adhesion by binding to extracellular matrix proteins, cell adhesion molecules, or other cells, thereby influencing cell migration, leukocyte recruitment, and tissue repair. ADGRE receptors can activate downstream signaling pathways through G protein-dependent or independent mechanisms, modulating intracellular signaling cascades and gene expression. Dysregulation of ADGRE signaling has been implicated in inflammatory disorders, autoimmune diseases, and cancer progression. Understanding the molecular mechanisms underlying ADGRE function provides insights into their roles in cellular physiology and disease pathology, offering potential targets for therapeutic intervention. Ongoing research continues to elucidate the complex functions of ADGRE receptors and their implications for human health.

Protein Structure

ADGRE receptors exhibit the typical features of adhesion GPCRs:

• Extracellular Domain: Contains adhesion motifs such as EGF-like domains, GPS (GPCR proteolytic site) domains, and mucin-like regions, which facilitate cell adhesion and interaction with the extracellular matrix.
• 7-Transmembrane Domain: This domain, characteristic of GPCRs, spans the cell membrane seven times and is essential for signal transduction.
• Intracellular Tail: The intracellular region has sites for interaction with G proteins and other intracellular signaling molecules, which are critical for initiating downstream signaling pathways.

Classification and Subtypes

The ADGRE subfamily includes several members:

• ADGRE1 (EMR1): EGF-like module-containing mucin-like hormone receptor-like 1
• ADGRE2 (EMR2): EGF-like module-containing mucin-like hormone receptor-like 2
• ADGRE3 (EMR3): EGF-like module-containing mucin-like hormone receptor-like 3
• ADGRE4 (EMR4): EGF-like module-containing mucin-like hormone receptor-like 4
• ADGRE5 (CD97): Cluster of Differentiation 97

These receptors are primarily distinguished by their extracellular domains and their specific roles in different tissues.

Function and Biological Significance

ADGRE receptors have diverse and significant roles:

1. Immune Response: ADGRE receptors are prominently expressed in immune cells and play roles in immune cell adhesion, migration, and activation, influencing immune surveillance and response.
2. Cell Adhesion: Facilitate interactions between cells and with the extracellular matrix, which is crucial for maintaining tissue integrity.
3. Signal Transduction: Initiate intracellular signaling pathways through G protein activation upon ligand binding, affecting cellular responses such as proliferation, differentiation, and migration.
4. Developmental Processes: Involved in developmental processes, particularly in the immune and nervous systems.

Interactions

ADGRE receptors interact with a variety of molecules:

1. Extracellular Matrix Proteins: Bind to matrix components like collagen and fibronectin, facilitating cell-matrix adhesion.
2. Other Cell Surface Receptors: Interact with integrins and other adhesion molecules, contributing to cell-cell communication.
3. G Proteins: Upon activation, interact with G proteins to initiate intracellular signaling cascades.
4. Intracellular Signaling Molecules: Engage with kinases, phosphatases, and other signaling proteins involved in cellular responses.

Clinical Significance

Alterations in ADGRE receptor function or expression are linked to various clinical conditions:

1. Immune Disorders: Dysregulation of ADGRE receptors can lead to autoimmune diseases and chronic inflammatory conditions due to their role in immune cell function.
2. Cancer: Abnormal expression of ADGRE receptors has been associated with tumor progression, metastasis, and tumor immune evasion.
3. Neurological Disorders: Involvement in neurodevelopment and neuroimmune interactions suggests roles in neurodevelopmental and neurodegenerative diseases.
4. Infectious Diseases: ADGRE receptors may play roles in host-pathogen interactions and the immune response to infections.

Summary

ADGRE receptors are part of the adhesion GPCR family and are essential for mediating cell adhesion, signaling, and immune responses. They are characterized by extended extracellular domains with adhesion motifs, a 7-transmembrane domain, and intracellular regions for signaling. ADGRE receptors play crucial roles in immune cell function, development, and cell adhesion. Dysregulation of these receptors is associated with immune disorders, cancer, neurological conditions, and infectious diseases. Understanding the structure, function, and interactions of ADGRE receptors provides valuable insights into their roles in health and disease.