G protein-coupled receptor

Definition

G protein-coupled receptors (GPCRs) are a large family of membrane proteins that play a critical role in cellular communication by transmitting signals from outside the cell to its interior. These receptors detect various ligands, such as hormones and neurotransmitters, triggering intracellular responses through the activation of associated G proteins, thus propagating the signal throughout the cell. GPCRs are involved in numerous physiological processes and are key players in many signaling pathways.

5 Must Know Facts For Your Next Test

1. GPCRs are one of the largest and most diverse groups of membrane proteins, with over 800 identified in humans.
2. Upon ligand binding, GPCRs undergo a conformational change, activating G proteins that can then influence various downstream signaling pathways.
3. G proteins are classified into three main families: Gs, Gi, and Gq, each of which activates different signaling cascades.
4. GPCR signaling is tightly regulated by desensitization mechanisms, including receptor phosphorylation and internalization, preventing overstimulation.
5. Many drugs target GPCRs due to their central role in mediating physiological responses, making them important in pharmacology and drug development.

Review Questions

• How do G protein-coupled receptors propagate signals within a cell after activation?
  • G protein-coupled receptors propagate signals by first binding to an external ligand, which causes a conformational change in the receptor. This change activates associated G proteins by exchanging GDP for GTP on the alpha subunit. The activated G protein then dissociates and interacts with downstream effectors, such as enzymes or ion channels, amplifying the signal inside the cell and leading to specific physiological responses.
• What roles do different types of G proteins play in signaling pathways initiated by GPCRs?
  • Different types of G proteins play distinct roles in GPCR-mediated signaling. For example, Gs proteins stimulate adenylate cyclase to increase cyclic AMP levels, leading to various cellular responses. In contrast, Gi proteins inhibit adenylate cyclase, decreasing cyclic AMP levels and having opposite effects. Meanwhile, Gq proteins activate phospholipase C, generating inositol trisphosphate and diacylglycerol as second messengers that promote calcium release and protein kinase activation. This diversity allows GPCRs to regulate a wide array of physiological processes.
• Evaluate the importance of GPCRs in drug development and their impact on treating diseases.
  • GPCRs are critically important in drug development because they represent a significant target for pharmacological intervention. Approximately 30-50% of all modern medicinal drugs act on GPCRs, addressing conditions like asthma, hypertension, depression, and more. Their widespread involvement in various signaling pathways means that modulating GPCR activity can lead to significant therapeutic effects. Understanding GPCR function and regulation can also help researchers design more selective drugs with fewer side effects, making them a focal point for advancing medical treatments.

Related terms

Ligand: A molecule that binds to a receptor to initiate a biological response, often acting as a signaling molecule.

G protein: A molecular switch that transmits signals from activated GPCRs to other intracellular effectors, regulating various cellular functions.

Second messenger: Intracellular signaling molecules that relay signals from receptors on the cell surface to target molecules inside the cell, amplifying the signal initiated by the receptor.