Membrane receptors are cellular gatekeepers, translating external signals into internal responses. They come in various types, each with unique structures and functions, allowing cells to respond to a diverse array of stimuli.

Signal transduction is the cellular communication highway, converting external cues into internal actions. This process involves a series of molecular events, including protein modifications like phosphorylation, which amplify and regulate the signal's journey through the cell.

Types and Functions of Membrane Receptors

Types of membrane receptors

• G protein-coupled receptors (GPCRs)
  • Largest family of membrane receptors includes rhodopsin and $\beta$-adrenergic receptors
  • Characterized by seven transmembrane domains that span the plasma membrane
  • Coupled to heterotrimeric G proteins on the intracellular side of the membrane
• Receptor tyrosine kinases (RTKs)
  • Single-pass transmembrane proteins that dimerize upon ligand binding
  • Possess intrinsic tyrosine kinase activity in their cytoplasmic domain which is activated by dimerization
  • Bind growth factors (epidermal growth factor), hormones (insulin), and cytokines (interferons)
• Ion channel receptors
  • Transmembrane proteins that form ion channels allowing ions to pass through the membrane
  • Can be ligand-gated (acetylcholine receptor) or voltage-gated (sodium channels)
  • Allow rapid ion flux across the membrane in response to specific stimuli like neurotransmitters or changes in membrane potential

Structure and function of receptors

• G protein-coupled receptors (GPCRs)
  • Structure: Seven transmembrane $\alpha$-helical domains, with an extracellular N-terminus that binds ligands and an intracellular C-terminus that interacts with G proteins
  • Function: Bind extracellular ligands (hormones, neurotransmitters, odorants) and activate intracellular G proteins, which then modulate the activity of effector proteins like enzymes (adenylyl cyclase) or ion channels (potassium channels)
• Receptor tyrosine kinases (RTKs)
  • Structure: Extracellular ligand-binding domain, single transmembrane domain, and cytoplasmic tyrosine kinase domain with multiple tyrosine residues
  • Function: Bind growth factors and other ligands, leading to receptor dimerization and autophosphorylation of tyrosine residues, which serve as docking sites for signaling proteins containing SH2 or PTB domains
• Ion channel receptors
  • Structure: Transmembrane proteins with a central pore that allows ion passage
    • Ligand-gated: Binding of a specific ligand (GABA, glycine) induces conformational changes that open the channel
    • Voltage-gated: Changes in membrane potential trigger channel opening or closing through the movement of voltage-sensing domains
  • Function: Rapidly change the membrane potential or intracellular ion concentrations in response to specific stimuli, enabling fast synaptic transmission or muscle contraction

Signal Transduction and Intracellular Responses

Process of signal transduction

• Signal transduction is the process by which cells convert extracellular signals (hormones, growth factors) into intracellular responses (changes in metabolism, gene expression)
• Involves a series of molecular events that relay the signal from the cell surface to the interior of the cell
• Key steps in signal transduction:
  1. Reception: Ligand binds to the extracellular domain of the receptor
  2. Transduction: Conformational changes in the receptor lead to activation of intracellular signaling molecules (G proteins, kinases)
  3. Amplification: Signaling cascades amplify the initial signal through sequential activation of enzymes (kinases, GTPases)
  4. Response: Activation of effector proteins (transcription factors, metabolic enzymes) leads to changes in cellular behavior or gene expression
• Allows cells to respond to their environment and communicate with each other

Protein modifications in signaling

• Protein modifications, particularly phosphorylation, play a crucial role in signal transduction by regulating protein activity and interactions
• Phosphorylation is the addition of a phosphate group to serine, threonine, or tyrosine residues catalyzed by protein kinases
• Kinases (receptor tyrosine kinases, MAP kinases) catalyze phosphorylation, while phosphatases (protein tyrosine phosphatases) remove phosphate groups
• Phosphorylation can:
  • Alter protein conformation and activity by inducing structural changes
  • Create binding sites for other signaling proteins containing SH2 or PTB domains
  • Regulate protein localization (nuclear translocation) and interactions (protein complexes)
• Signaling cascades often involve a series of phosphorylation events, allowing for signal amplification and integration of multiple signals
• Dephosphorylation by phosphatases helps terminate signaling and maintains cellular homeostasis by counteracting kinase activity