APLNR - Apelin receptor | Elisa - Clia - Antibody - Protein

Background:

APLNR, also known as the Apelin receptor or APJ, is a G protein-coupled receptor (GPCR) that was initially identified based on its sequence similarity to the angiotensin receptor. APLNR is encoded by the APLNR gene in humans and is widely expressed in various tissues, including the heart, lungs, kidneys, and central nervous system. This receptor is known to bind to the endogenous peptide ligand apelin and plays a significant role in numerous physiological processes.

Protein Structure:

• GPCR Structure: APLNR is a seven-transmembrane domain receptor typical of the GPCR family. These domains are connected by extracellular and intracellular loops, with an extracellular N-terminus and an intracellular C-terminus.
• Ligand-Binding Domain: The receptor's extracellular regions are crucial for binding to its ligand, apelin.
• Intracellular Signaling Domains: The intracellular loops and the C-terminus are involved in coupling with G proteins and initiating downstream signaling pathways.

Classification and Subtypes:

APLNR is classified as a class A (rhodopsin-like) GPCR. Although there are no major subtypes of the APLNR receptor itself, the receptor can interact with various isoforms of its ligand apelin, such as apelin-13, apelin-17, and apelin-36, which can have differing physiological effects.

Function and Biological Significance:

• Cardiovascular Regulation: APLNR plays a critical role in cardiovascular homeostasis, including blood pressure regulation, cardiac contractility, and fluid homeostasis. It exerts vasodilatory and cardioprotective effects.
• Angiogenesis: The receptor is involved in the regulation of angiogenesis, the process by which new blood vessels form from existing vessels, which is vital for tissue growth and repair.
• Fluid Homeostasis: APLNR regulates water balance and fluid homeostasis in the body by influencing renal function and the release of antidiuretic hormone (ADH).
• Energy Metabolism: It plays a role in energy metabolism and adipogenesis, influencing body weight and fat distribution.
• Central Nervous System: APLNR is implicated in various central nervous system functions, including neuroprotection and neurodevelopment.

Interactions:

• Apelin: The primary endogenous ligand for APLNR. Binding of apelin to APLNR activates various intracellular signaling cascades, including those involving G proteins and β-arrestins.
• G Proteins: Upon ligand binding, APLNR primarily couples with Gαi proteins, leading to inhibition of adenylate cyclase and a decrease in cyclic AMP (cAMP) levels.
• β-Arrestins: These proteins are involved in receptor desensitization, internalization, and signaling independent of G proteins.

Clinical Issues:

• Cardiovascular Diseases: Dysregulation of the apelin-APLNR axis is associated with hypertension, heart failure, and other cardiovascular disorders. Apelin has been explored as a potential therapeutic target for treating these conditions.
• Metabolic Disorders: Alterations in APLNR signaling are linked to metabolic diseases such as obesity and diabetes. Apelin mimetics or antagonists could be potential therapeutic agents.
• Cancer: APLNR and its ligand apelin are involved in tumor angiogenesis and cancer progression. Overexpression of APLNR has been observed in various cancers, making it a potential target for cancer therapy.
• Neurodegenerative Diseases: There is emerging evidence of APLNR's role in neuroprotection, suggesting potential therapeutic implications for neurodegenerative diseases such as Alzheimer's disease.

Summary:

APLNR is a critical GPCR involved in a wide array of physiological processes, particularly in cardiovascular regulation, fluid homeostasis, and energy metabolism. The receptor's interaction with its ligand apelin mediates important signaling pathways that influence heart function, blood vessel formation, and metabolic balance. Dysregulation of the apelin-APLNR axis is implicated in several diseases, including cardiovascular diseases, metabolic disorders, cancer, and neurodegenerative diseases. Understanding the detailed mechanisms of APLNR signaling and its interactions with various ligands and intracellular proteins can provide insights into novel therapeutic strategies for these conditions.