ADGRV1-Adhesion G-protein coupled receptor V1 |Elisa - Clia - Antibody - Protein

Background

Adhesion G-protein coupled receptor V1 (ADGRV1), also known as GPR98, is a member of the adhesion GPCR family. ADGRV1 is a large transmembrane protein with an extracellular domain containing multiple adhesion motifs, a seven-transmembrane domain characteristic of G protein-coupled receptors (GPCRs), and an intracellular domain involved in signaling. ADGRV1 is primarily expressed in the inner ear and is essential for auditory function. It plays a crucial role in the development and maintenance of stereocilia, the specialized hair-like structures in the inner ear that detect sound vibrations and convert them into electrical signals. Mutations in the ADGRV1 gene are associated with various forms of hereditary hearing loss, including Usher syndrome type IIC and nonsyndromic deafness. These mutations disrupt the normal function of ADGRV1, leading to structural abnormalities in the stereocilia or impairment of signal transduction in the inner ear.

Protein Structure

ADGRV1 has the hallmark features of adhesion GPCRs but is notable for its large size and complex structure:

• Extracellular Domain: Contains multiple adhesion domains, including Calx-beta domains, which are implicated in calcium ion binding, and various cadherin repeats that facilitate cell-cell adhesion.
• 7-Transmembrane Domain: This domain is essential for transmitting signals from the extracellular environment to the intracellular milieu.
• Intracellular Tail: Contains several sites for interaction with intracellular signaling molecules, critical for initiating downstream signaling pathways.

Classification and Subtypes

ADGRV1 is a unique and singular member within its classification, distinguished by its specific structural domains and large size. It does not have subtypes but is categorized within the broader adhesion GPCR family.

Function and Biological Significance

ADGRV1 plays significant roles in various biological processes:

1. Auditory and Vestibular Function: Critical for the development and maintenance of the inner ear structures, influencing hearing and balance.
2. Synaptic Development and Function: Involved in the formation and function of synapses in the nervous system, affecting neural connectivity and signaling.
3. Cell Adhesion and Signal Transduction: Facilitates interactions between cells and the extracellular matrix, and initiates intracellular signaling pathways upon ligand binding.
4. Neural Development: Essential for proper neural development, influencing processes such as neurite outgrowth and neural patterning.

Interactions

ADGRV1 interacts with a variety of molecules to perform its functions:

1. Calcium Binding Proteins: Interacts with proteins involved in calcium signaling, which is critical for many cellular processes.
2. Other Cell Surface Receptors: Engages with other adhesion molecules and integrins to mediate cell-cell and cell-matrix interactions.
3. G Proteins: Activates G proteins upon ligand binding, leading to intracellular signaling cascades that regulate various cellular responses.
4. Intracellular Signaling Molecules: Interacts with kinases, phosphatases, and other intracellular proteins to modulate cellular functions.

Clinical Significance

Mutations and dysregulation of ADGRV1 are associated with several clinical conditions:

1. Usher Syndrome Type II: Mutations in the ADGRV1 gene are a major cause of Usher syndrome type II, a disorder characterized by hearing loss and retinitis pigmentosa, leading to progressive vision loss.
2. Epilepsy: Some studies suggest a link between ADGRV1 mutations and epilepsy, though the mechanisms are not fully understood.
3. Balance Disorders: Given its role in the vestibular system, ADGRV1 dysfunction can lead to balance and coordination issues.

Summary

ADGRV1, or Very Large G-protein coupled Receptor 1, is an essential member of the adhesion GPCR family with critical roles in sensory functions, particularly in hearing and balance, as well as neural development and synaptic function. This receptor is characterized by its large extracellular domain with multiple adhesion motifs, a 7-transmembrane domain, and an intracellular tail for signaling. Dysregulation or mutations in ADGRV1 are linked to significant clinical conditions, including Usher syndrome type II and potentially epilepsy and balance disorders. Understanding ADGRV1's structure, function, and interactions is vital for unraveling its roles in health and disease.