Cell Signaling: Cell Surface Receptors

Cell Surface Receptors

  • Receptors for lipophobic messengers (water-soluble, cannot cross the cell membrane).
  • Three major families:
    • Ion channel-linked receptors
    • Enzyme-linked receptors
    • G protein-linked receptors

Signal Transduction

  • Messenger binds to receptor $\rightarrow$ cell response.
  • Aims to produce and amplify the signal.

Phosphorylation

  • Regulated by kinases (add phosphate) and phosphatases (remove phosphate).
  • Occurs mainly on serine, threonine, and tyrosine amino acids.
  • Alters protein activity by causing conformational changes.
  • Acts as a molecular switch, controlling enzyme activity.
  • Prevents futile cycles by coordinating synthesis and degradation.

Generalized Structure of Cell Surface Receptors

  • Integral membrane proteins with three domains:
    • Ligand-binding domain (extracellular)
    • Transmembrane domain (anchors receptor)
    • Cytoplasmic/intracellular domain (effector region)
  • Ligand binding activates the effector region, relaying the signal.

Types of Cell Surface Receptors and Their Mechanisms

  • Activated receptors induce responses by:
    • Changing ion movement.
    • Altering phosphorylation states of enzymes/proteins.
  • Differ from intracellular receptors that change gene expression.

1. Ion Channel-Linked Receptors

  • Ligand binding opens or closes ion channels, changing ion movement.
  • Receptor and channel are the same protein in fast channels.
  • Also called ligand-gated channels or transmitter-gated ion channels.
  • Specific for particular ions, determining plasma membrane permeability.
  • Two categories:
    *Fast Channels: Receptor and channel are the same protein; immediate action.
    *Slow Channels: Receptor and channel are separate proteins linked by G proteins; slower action.
  • Involved in rapid synaptic signaling.
  • Ion movement changes electrical properties or interacts with intracellular proteins.
  • Example: Calcium channels affecting metabolism, hormone secretion, and muscle contraction.
  • Binding of ligand to the receptor leads to the opening of the ion channel.
  • Change in the transport of iron through the channel will cause the target response.
  • Neurotransmitter acetylcholine is a messenger.
  • Target for many drugs (e.g., barbiturates) and implicated in diseases like schizophrenia and Parkinson's.
  • Composed of polypeptide chains (e.g., alpha, beta, delta, gamma) encoded by different but homologous genes.

2. Enzyme-Linked Receptors

  • Associated with tyrosine kinases (phosphorylate proteins on tyrosine residues).
  • Two types:
    • Receptor tyrosine kinases: Receptor itself has kinase activity.
    • Tyrosine kinase-associated receptors: Receptor associates with a separate tyrosine kinase.
  • Ligand binding activates the receptor, leading to phosphorylation of target proteins.
  • Action is direct: changes phosphorylation state of signaling molecules.
  • Examples: insulin signaling and growth hormone signaling.
  • In the absence of the ligand, these receptors are inactive.
  • Signaling molecules on the tyrosine residue then relay the signal away from the receptor.
  • Phosphorylation of the protein change activity to bring response.
  • Some pathways alter gene expression.

3. G Protein-Coupled Receptors

  • Linked to G proteins (GTP-binding proteins) on the intracellular side.
  • G protein activation conveys the message to the next component.
  • Effectors are either ion channels or amplifier enzymes (linked to second messenger systems).
  • Ligand binding activates the G protein, which relays the signal.
  • Trimeric G proteins (alpha, beta, gamma subunits) are inactive when bound to GDP.
  • Receptor activates G protein $\rightarrow$ GDP replaced by GTP $\rightarrow$ alpha subunit dissociates and activates ion channel.
  • Associated with slow ligand-gated channels or amplifier enzymes.
  • Example: Adenylate cyclase synthesizes cyclic AMP from ATP; cyclic AMP activates protein kinase A, which phosphorylates other proteins.
  • Amplifier enzymes are associated with the generation of a second passenger system.

Summary of Cell Surface Receptors

  • Ion channel-linked: change ion movement.
  • G protein-linked: change ion movement or phosphorylation.
  • Enzyme-linked: change phosphorylation of key enzymes/proteins.