Biology I - Cell Biology Lectures 2025-2026

Faculty Information
  • Instructor: Varvara Trachana, Associate Professor of Medical Biology - Cell Biology
  • Position: Director of the Laboratory of Biology
Study Material
  • Topic: Cellular Communication II
  • Reference: Chapter 15, Basic Principles of Cell Biology - Alberts et al.
Lecture Structure
  1. General principles of cell signaling
    • Cells communicate to coordinate behavior, respond to environmental changes, and maintain homeostasis.
    • This involves a sequence of events: reception of a signal, transduction of the signal within the cell, and a cellular response.
    • Signal termination mechanisms are crucial for stopping responses and preparing for new signals.
  2. Ion-Channel coupled receptors
    • Also known as ligand-gated ion channels.
    • These receptors convert chemical signals into electrical signals.
    • Upon binding of a neurotransmitter or other ligand, they open or close, allowing specific ions (e.g., Na+, K+, Ca++, Cl-) to flow across the plasma membrane.
    • This rapid ion movement changes the membrane potential, which is critical for nerve impulse transmission and muscle contraction.
  3. G-protein coupled receptors
  4. Enzyme-linked receptors
    • These receptors typically possess intrinsic enzyme activity or associate directly with enzymes.
    • Ligand binding activates the enzyme, often a kinase, leading to phosphorylation cascades within the cell.
    • They typically mediate responses related to cell growth, proliferation, survival, and differentiation.
  5. Signal transduction - KINASES
G-Protein Coupled Receptors (GPCRs)
Structural Characteristics
  • GPCRs consist of a continuous polypeptide chain that crosses the membrane seven times.
    • These seven transmembrane domains are α-helices, forming a compact structure within the membrane.
    • The extracellular loops bind the specific ligand, while the intracellular loops and C-terminal tail interact with G-proteins.
  • They include receptors like:
    • Eye rhodopsin (light detection)
    • Nose olfactory receptors (smell detection)
    • Yeast mating receptors (cell recognition)
  • They are considered a primitive family of proteins, with bacterial versions involved in nutrient detection (though these do not associate with G-proteins, as G-proteins are not present in bacteria).
  • GPCRs form the largest family of receptors with hundreds of members, responding to various signals like:
    • Hormones (e.g., adrenaline, glucagon)
    • Neurotransmitters (e.g., acetylcholine, dopamine)
    • Local mediators (e.g., proteins, peptides, fatty acids, prostaglandins)
    • Light, odorants, and even taste molecules.
Mechanism of Action
  • Upon binding with the extracellular signal (ligand), GPCRs undergo a conformational change that enables interaction with the associated heterotrimeric G-protein on the cytoplasmic side of the membrane.
    • This conformational change in the GPCR acts as a guanine nucleotide exchange factor (GEF), promoting the G-protein to exchange bound GDP for GTP.
  • Activation leads to:
    • Stimulation of G-proteins, initiating the downstream signaling cascade.
G-Protein Structure and Function
  • G-proteins are made up of three subunits: α, β, and γ.
    • The α and γ subunits are typically attached to the membrane by covalently linked lipid tails (myristoylation or prenylation), anchoring the complex to the inner leaflet of the plasma membrane.
  • In resting conditions (inactive state), the α subunit is bound to GDP and is associated with the βγ complex.
  • Activation Process:
    1. Binding of the ligand to the receptor activates the GPCR.
    2. The activated GPCR induces a conformational change in the associated G-protein, causing the α subunit to release its bound GDP and bind GTP (a higher affinity for GTP develops).
    3. The activated G-protein then splits into two signaling molecules:
      • The GTP-bound α subunit.
      • The βγ complex (which remains associated).
    4. Both the GTP-bound α subunit and the βγ complex diffuse laterally across the membrane, interacting with various target proteins (e.g., enzymes, ion channels) to transmit the signal downstream.
Regulation of G-Protein Activation
  • The duration of G-protein activation is determined by the intrinsic enzymatic activity of the α subunit. As a GTP hydrolase (GTPase), it hydrolyzes GTP back to GDP.
    • This hydrolysis leads to:
      • Re-association of the now GDP-bound α subunit with the βγ complex, reforming the inactive heterotrimeric G-protein.
      • Termination of the signal transmission (this usually occurs seconds after activation, ensuring transient responses).
  • Both α and βγ subunits can independently regulate target proteins, diversifying the cellular response.
  • Further regulation involves receptor desensitization, where GPCRs can be phosphorylated by G-protein receptor kinases (GRKs) and subsequently bound by arrestin proteins, leading to uncoupling from G-proteins or receptor internalization.
Clinical Implications of GPCRs
Cholera
  • Caused by Vibrio cholerae, which produces the cholera toxin BFS affecting the G-protein α subunit (specifically Gs α, a stimulatory G-protein).
  • The toxin modifies the α subunit covalently, preventing it from hydrolyzing GTP to GDP.
  • This results in continuous activation of Gs α, locking it in its