ADGRL - Adhesion G protein-coupled receptor L | Elisa - Clia - Antibody - Protein

Background

Adhesion G protein-coupled receptor L (ADGRL), also known as LPHN (latrophilin), is a member of the adhesion GPCR family. ADGRL receptors are characterized by a large extracellular domain containing multiple domains involved in cell adhesion, a seven-transmembrane domain typical of G protein-coupled receptors (GPCRs), and an intracellular domain that interacts with G proteins and other signaling molecules.ADGRL receptors are involved in various physiological processes including neuronal development, synapse formation, and neurotransmitter release. They are particularly important in the central nervous system, where they regulate neuronal migration, axon guidance, and synaptic transmission.The natural ligands for ADGRL receptors are diverse and include extracellular matrix proteins, such as α-latrotoxin (hence the name latrophilin), as well as other cell adhesion molecules. These ligands mediate interactions between cells and their environment, contributing to cell adhesion and signaling processes.Mutations in ADGRL genes have been associated with neurodevelopmental disorders, including attention-deficit/hyperactivity disorder (ADHD), autism spectrum disorders, and intellectual disability. Additionally, dysregulation of ADGRL expression has been implicated in various cancers.

Protein Structure

ADGRL receptors possess the characteristic structural features of adhesion GPCRs:

• Extracellular Domain: This domain contains several adhesion motifs, such as lectin-like domains, olfactomedin-like domains, and GPS (GPCR proteolytic site) domains, which facilitate interactions with extracellular matrix components and other cells.
• 7-Transmembrane Domain: This domain traverses the cell membrane seven times and is essential for the receptor's ability to transmit signals inside the cell.
• Intracellular Tail: The intracellular region includes sites for interacting with G proteins and other signaling molecules, which are essential for initiating intracellular signaling cascades.

Classification and Subtypes

The ADGRL subfamily includes several members:

• ADGRL1 (Latrophilin 1)
• ADGRL2 (Latrophilin 2)
• ADGRL3 (Latrophilin 3)

These receptors are distinguished by their unique extracellular domain structures and their specific tissue expression patterns.

Function and Biological Significance

ADGRL receptors are involved in a variety of biological processes:

1. Synapse Formation and Maintenance: Play critical roles in the development and maintenance of synapses in the nervous system, affecting neural connectivity and communication.
2. Cell Adhesion: Mediate interactions between cells and the extracellular matrix, contributing to tissue integrity and organization.
3. Signal Transduction: Initiate intracellular signaling pathways through G protein activation upon ligand binding, affecting various cellular responses such as proliferation, differentiation, and migration.
4. Developmental Processes: Essential for proper embryonic development, including neural and vascular development.
5. Neural Function: Involved in the regulation of neuronal activity and neurotransmitter release, influencing neural plasticity and behavior.

Interactions

ADGRL receptors interact with a variety of molecules to execute their functions:

1. Extracellular Matrix Proteins: Bind to components such as laminin and fibronectin, 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

Dysfunction or abnormal expression of ADGRL receptors is associated with various diseases:

1. Neurodevelopmental Disorders: Alterations in ADGRL receptors have been linked to conditions such as autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD).
2. Cancer: Dysregulation of ADGRL receptors may contribute to tumor progression and metastasis.
3. Cardiovascular Diseases: Implicated in vascular development and function, with potential roles in conditions such as atherosclerosis.
4. Neurological Disorders: Mutations and abnormal expression can contribute to neurodegenerative diseases and epilepsy.
5. Psychiatric Disorders: Abnormal ADGRL receptor function has been associated with psychiatric conditions, including schizophrenia and bipolar disorder.

Summary

ADGRL receptors, part of the adhesion GPCR family, are crucial for mediating cell adhesion, signaling, and various physiological processes. These receptors, characterized by their extended extracellular domains with adhesion motifs, 7-transmembrane domains, and intracellular signaling regions, play significant roles in synapse formation, cell adhesion, signal transduction, development, and neural function. Dysregulation of ADGRL receptors is associated with a range of disorders, including neurodevelopmental and psychiatric disorders, cancer, cardiovascular diseases, and neurological conditions. Understanding the structure, function, and interactions of ADGRL receptors provides valuable insights into their roles in health and disease.