ADGRD - Adhesion G-protein coupled receptor D | Elisa - Clia - Antibody - Protein

Background

Adhesion G protein-coupled receptor D (ADGRD) is a member of the adhesion G protein-coupled receptor (GPCR) family, characterized by its unique structure featuring a large extracellular domain responsible for cell-cell and cell-matrix interactions. ADGRD receptors play crucial roles in various physiological processes, including neuronal development, immune response regulation, and tissue morphogenesis. They mediate adhesion by binding to extracellular matrix proteins, cell adhesion molecules, or other cells, thereby influencing cell migration, axon guidance, and tissue organization. ADGRD receptors can activate downstream signaling pathways through G protein-dependent or independent mechanisms, modulating intracellular signaling cascades and gene expression. Dysregulation of ADGRD signaling has been implicated in neurological disorders, immune system dysfunction, and cancer progression. Understanding the molecular mechanisms underlying ADGRD 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 ADGRD receptors and their implications for human health.

Protein Structure

ADGRD receptors share the typical features of adhesion GPCRs:

• Extracellular Domain: Contains multiple adhesion motifs, including cadherin repeats, EGF-like domains, and thrombospondin repeats, which facilitate interactions with the extracellular matrix and other cells.
• 7-Transmembrane Domain: A hallmark of GPCRs, this domain spans the cell membrane seven times, enabling signal transduction.
• Intracellular Tail: The intracellular region contains sites for interacting with G proteins and other intracellular signaling molecules, crucial for initiating downstream signaling pathways.

Classification and Subtypes

The ADGRD subfamily includes the following members:

• ADGRD1 (GPR133)
• ADGRD2 (GPR144)

These receptors are classified based on their specific extracellular adhesion domains and tissue-specific expression patterns.

Function and Biological Significance

ADGRD receptors play several key roles in physiological processes:

1. Cell Adhesion: Mediate cell-cell and cell-matrix interactions, essential for tissue integrity and organization.
2. Signal Transduction: Initiate intracellular signaling pathways via G protein activation upon binding of extracellular ligands, influencing various cellular responses such as proliferation, differentiation, and migration.
3. Developmental Processes: Involved in embryonic development, particularly in neural and vascular development.
4. Immune Regulation: Play roles in immune cell adhesion and migration, impacting immune surveillance and response.

Interactions

ADGRD receptors interact with various molecules to perform their functions:

1. Extracellular Matrix Proteins: Bind to components such as collagen, fibronectin, and laminin, facilitating cell-matrix adhesion.
2. Other Cell Surface Receptors: Interact with integrins and other adhesion molecules to mediate cell-cell communication.
3. G Proteins: Activate G proteins upon ligand binding, leading to intracellular signaling cascades.
4. Intracellular Signaling Molecules: Engage with kinases, phosphatases, and other signaling proteins to modulate cellular responses.

Clinical Significance

Alterations in ADGRD receptor function or expression are linked to various diseases:

1. Cancer: Dysregulation of ADGRD receptors has been associated with tumor progression, metastasis, and angiogenesis.
2. Neurological Disorders: Mutations and abnormal expression of ADGRD receptors can contribute to neurodevelopmental and neurodegenerative diseases.
3. Cardiovascular Diseases: Involved in vascular development and integrity, with implications in conditions like atherosclerosis and hypertension.
4. Immune Disorders: Affect immune cell function and inflammation, potentially influencing autoimmune diseases and chronic inflammatory conditions.

Summary

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