G-protein coupled receptors

Definition

G-protein coupled receptors (GPCRs) are a large family of membrane proteins that play a crucial role in cellular signaling by interacting with G-proteins. These receptors are involved in various physiological processes, including hormone action and signal transduction, making them essential for transmitting signals from outside the cell to the inside. GPCRs respond to a variety of ligands, including hormones and neurotransmitters, which initiate a cascade of intracellular responses.

5 Must Know Facts For Your Next Test

1. GPCRs are characterized by their seven transmembrane alpha-helices, which span the cell membrane and create a binding pocket for ligands.
2. When a ligand binds to a GPCR, it causes a conformational change that activates an associated G-protein by exchanging GDP for GTP.
3. The activated G-protein can then interact with various effectors, such as enzymes or ion channels, leading to the production of second messengers like cAMP or IP3.
4. GPCRs are implicated in numerous diseases and conditions, making them important drug targets; approximately 30-40% of modern medicinal drugs work by targeting GPCRs.
5. Desensitization of GPCRs occurs when prolonged exposure to a ligand decreases receptor activity, preventing overstimulation and allowing cells to adapt to continuous signaling.

Review Questions

• How do G-protein coupled receptors activate intracellular signaling pathways upon ligand binding?
  • When a ligand binds to a G-protein coupled receptor, it induces a conformational change in the receptor. This change activates an associated G-protein by exchanging GDP for GTP. The activated G-protein then dissociates into its subunits, which can interact with various target proteins inside the cell, triggering intracellular signaling pathways that result in a specific cellular response.
• Discuss the role of second messengers in the signaling cascade initiated by G-protein coupled receptors.
  • Second messengers are crucial components of the signaling cascade initiated by G-protein coupled receptors. Once a GPCR activates a G-protein, this can lead to the production of second messengers like cyclic AMP (cAMP) or inositol trisphosphate (IP3). These second messengers amplify the signal within the cell and activate additional downstream signaling pathways that result in various physiological responses, such as changes in gene expression or cellular metabolism.
• Evaluate the significance of G-protein coupled receptors as drug targets in modern medicine and how their dysfunction can contribute to disease.
  • G-protein coupled receptors are highly significant as drug targets due to their involvement in many physiological processes and diseases. Approximately 30-40% of current medications act on GPCRs, highlighting their potential for therapeutic intervention. Dysfunction of these receptors can lead to various health issues, including metabolic disorders, neurological diseases, and cancers. Therefore, understanding GPCR function and regulation is essential for developing new drugs that can effectively target these important receptors.

Related terms

Ligand: A molecule that binds to a receptor, such as a hormone or neurotransmitter, to initiate a cellular response.

Second Messenger: Intracellular signaling molecules that are generated in response to the activation of GPCRs and amplify the signal within the cell.

Signal Transduction Pathway: A series of molecular events and interactions that lead to a cellular response after a receptor is activated.