ADGRG - Adhesion G-protein coupled receptor G | Elisa - Clia - Antibody - Protein

Background

Members of this family exhibit elongated N-termini and harbor multiple functional domains. They are implicated in immune system functions and central nervous system activities. Through alternative splicing, numerous transcript variants are generated, encoding diverse isoforms.ADGRG1 is a member of the G protein-coupled receptor family and regulates brain cortical patterning. Binds specifically to transglutaminase 2, a component of tissue and tumor stroma implicated as an inhibitor of tumor progression. Mutations in this gene are associated with a brain malformation known as bilateral frontoparietal polymicrogyria. is linked to diseases such as Cortical Dysplasia, Complex, With Other Brain Malformations .ADGRG2 is a G protein-coupled receptor family member recognized as an epididymis-specific transmembrane protein. It may undergo proteolytic processing, as indicated by the presence of a motif known to facilitate protein scission in certain family members

Protein Structure

ADGRG receptors share common structural features typical of adhesion GPCRs:

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

Classification and Subtypes

The ADGRG subfamily includes several members:

• ADGRG1 (GPR56)
• ADGRG2 (GPR64)
• ADGRG3 (GPR97)
• ADGRG4 (GPR112)
• ADGRG5 (GPR114)
• ADGRG6 (GPR126)

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

Function and Biological Significance

ADGRG receptors have diverse and significant roles:

1. Cell Adhesion: Facilitate interactions between cells and with the extracellular matrix, crucial for maintaining tissue integrity and organization.
2. Signal Transduction: Initiate intracellular signaling pathways through G protein activation upon ligand binding, affecting cellular responses such as proliferation, differentiation, and migration.
3. Developmental Processes: Play important roles in embryonic development, including neural, vascular, and organ development.
4. Immune Regulation: Involved in the regulation of immune cell adhesion, migration, and function, impacting immune surveillance and response.
5. Nervous System: Involved in the development and maintenance of the nervous system, affecting neural migration, axon guidance, and synapse formation.

Interactions

ADGRG receptors interact with a variety of 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 ADGRG receptor function or expression are linked to various diseases:

1. Cancer: Dysregulation of ADGRG receptors has been associated with tumor progression, metastasis, and angiogenesis.
2. Neurological Disorders: Mutations and abnormal expression of ADGRG 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.
5. Musculoskeletal Disorders: Implicated in the development and maintenance of musculoskeletal tissues, with potential roles in disorders like muscular dystrophy.

Summary

ADGRG 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. ADGRG receptors play crucial roles in cell adhesion, signal transduction, development, immune regulation, and nervous system function. Dysregulation of these receptors is associated with cancer, neurological disorders, cardiovascular diseases, immune disorders, and musculoskeletal disorders. Understanding the structure, function, and interactions of ADGRG receptors provides insights into their roles in health and disease.