GPCR Signaling
GPCR signaling occurs when a ligand binds to the extracellular domain of the receptor, causing a conformational change in the receptor that activates the intracellular G protein. The G protein is a heterotrimeric complex made up of alpha, beta, and gamma subunits. Activation of the G protein leads to the release of the alpha subunit, which then activates an effector enzyme or ion channel. This results in a downstream signaling response, such as the activation of an intracellular second messenger or the opening of an ion channel.
Also read: G-Protein Coupled Receptor
G proteins come in a variety of forms, including Gs, Gi, and Gq. Each type of G protein stimulates a particular effector enzyme or ion channel. For instance, when Gs proteins are activated, adenylate cyclase is also activated. This enzyme turns ATP into cyclic AMP (cAMP), a second messenger that has a variety of intracellular destinations. Gi protein activation inhibits adenylate cyclase, whereas Gq protein activation activates phospholipase C, resulting in the synthesis of inositol triphosphate (IP3) and diacylglycerol (DAG).
Also Read: Inositol and Diacylglycerol Pathway
GPCR signaling is regulated by several mechanisms, including receptor desensitization, receptor internalization, and receptor recycling. Desensitization refers to the process by which the receptor becomes less responsive to ligand binding after prolonged or excessive activation. Internalization is the process by which the receptor is internalized into the cell and recycled back to the cell surface. This process can either enhance or inhibit signaling, depending on the specific receptor and signaling pathway.
GPCR signaling plays a crucial role in many physiological processes, including neurotransmitter and hormone signaling, immune system activation, and cardiovascular regulation. Dysregulation of GPCR signaling has been implicated in various diseases, including cancer, diabetes, and cardiovascular and neurological disorders.
GPCR Structure
- GPCRs are composed of seven transmembranes (TM) domains, which are connected by intracellular and extracellular loops.
- The TM domains are composed of alpha helices that are oriented perpendicular to the cell membrane.
- The intracellular loops and the C-terminal tail of the GPCR interact with intracellular signaling proteins, such as G proteins, arrestins, and other effector proteins.
- The extracellular domain of the GPCR is exposed to the extracellular environment and is responsible for ligand binding.
GPCR Signaling Pathway
G protein-coupled receptors (GPCRs) are a type of cell surface receptor that is activated by ligands, such as hormones, neurotransmitters, and other signaling molecules. When activated, GPCRs initiate a signaling cascade through a process called G protein-coupled receptor signaling.