ADGRA - Adhesion G protein-coupled receptor A | Elisa - Clia - Antibody - Protein

Background

Adhesion G protein-coupled receptor A (ADGRA) is a subgroup of the adhesion G protein-coupled receptor (GPCR) family that plays critical roles in cell-cell and cell-matrix interactions. ADGRA receptors typically consist of a large extracellular domain responsible for ligand binding, a seven-transmembrane domain, and an intracellular domain linked to G protein signaling pathways. These receptors are involved in diverse biological processes, including cell adhesion, migration, angiogenesis, and neuronal development. ADGRA receptors mediate adhesion through interactions with extracellular matrix components, cell adhesion molecules, or other cells. Dysregulation of ADGRA signaling has been implicated in various diseases, including cancer metastasis, cardiovascular disorders, and neurological conditions. Research on ADGRA receptors provides insights into their roles in cellular physiology and pathology, offering potential targets for therapeutic intervention in a wide range of diseases. Ongoing studies continue to elucidate the molecular mechanisms underlying ADGRA receptor function and their implications for human health.

Protein Structure

ADGRA receptors share common structural features typical of adhesion GPCRs:

• Extracellular Domain: Contains various motifs for cell adhesion, such as cadherin, lectin, and EGF-like domains, which facilitate interactions with other cells and the extracellular matrix.
• 7-Transmembrane Domain: This domain is characteristic of GPCRs and spans the cell membrane seven times, allowing the receptor to transmit signals from outside the cell to its interior.
• Intracellular Tail: Contains sites for interaction with G proteins and other intracellular signaling molecules.

Classification and Subtypes

The ADGRA subfamily consists of several receptors, classified based on their structural and functional properties:

• ADGRA1 (GPR123)
• ADGRA2 (GPR124)
• ADGRA3 (GPR125)

These receptors differ in their specific extracellular adhesion domains and tissue distribution but share common signaling mechanisms.

Function and Biological Significance

ADGRA receptors are involved in various crucial biological processes:

1. Cell Adhesion: Mediate interactions between cells and with the extracellular matrix, essential for tissue integrity and architecture.
2. Developmental Processes: Play roles in embryogenesis, particularly in neural development and vascular formation.
3. Immune Response: Involved in the regulation of immune cell migration and adhesion, influencing immune surveillance and response.
4. Signal Transduction: Transduce extracellular signals through G protein-mediated pathways, affecting cellular responses such as proliferation, differentiation, and migration.

Interactions

ADGRA receptors interact with a variety of extracellular and intracellular molecules:

1. Extracellular Matrix Proteins: Bind to matrix components such as collagen and fibronectin, facilitating cell-matrix interactions.
2. Cell Surface Molecules: Interact with other cell surface receptors, contributing to cell-cell adhesion and communication.
3. G Proteins: Activate G proteins upon ligand binding, initiating intracellular signaling cascades that regulate various cellular functions.
4. Intracellular Signaling Molecules: Engage with kinases, phosphatases, and other signaling proteins to modulate cellular responses.

Clinical Significance

Dysregulation or mutations in ADGRA receptors are associated with several clinical conditions:

1. Cancer: Altered expression and function of ADGRA receptors have been linked to tumor progression, metastasis, and angiogenesis.
2. Developmental Disorders: Mutations in ADGRA genes can lead to congenital abnormalities due to their critical roles in embryonic development.
3. Neurological Diseases: Implicated in neurodevelopmental disorders and neurodegenerative diseases due to their functions in the nervous system.
4. Cardiovascular Diseases: Play roles in vascular development and integrity, with potential implications in conditions like atherosclerosis and hypertension.

Summary

ADGRA receptors are a subfamily of adhesion GPCRs that play critical roles in cell adhesion, signaling, and development. These receptors are characterized by their extracellular adhesion domains, 7-transmembrane structure, and intracellular signaling capabilities. They are involved in essential biological processes, including tissue integrity, immune responses, and neural development. Dysregulation of ADGRA receptors is associated with various diseases, including cancer, developmental disorders, and cardiovascular conditions. Understanding the structure, function, and interactions of ADGRA receptors provides valuable insights into their roles in health and disease.