Biology I - Cell Biology Lectures 2025-2026

Biology I - Cell Biology Lectures 2025-2026

Faculty of Medicine

Varvara Trachana, Associate Professor of Medical Biology - Cell Biology, Director of the Laboratory of Biology

Study

Cellular Communication I

Chapter 15: Basic Principles of Cell Biology - Alberts et al.

Introduction to Cellular Responses

  • Saccharomyces cells (a type of yeast) respond to mating factors secreted by neighboring yeast cells by growing a protrusion aimed towards the source of the mating factor.
  • In multicellular organisms, cellular communication is more complex. Cells must interpret various signals they receive from other cells to adjust their behavior accordingly.

Key Terminology Related to Embryogenesis

  • Polar body
  • Pronuclei
  • Day 1 - Fertilization
  • Zona
  • Blastomere
  • Inner cell
  • Tight cell junction
  • Day 2 - Cleavage, Day 3 Compaction
  • Bilaminar disc
  • Epiblast
  • Hypoblast
  • Trophoblast
  • Day 12 - Bilaminar disc formation
  • Day 9 - Cell mass differentiates into
    • Ectoderm
    • Mesoderm
    • Primitive streak
    • Endoderm
    • Exocoelom
    • Chorion
  • Day 4 - Differentiation; Blastocoelic cavity forms
  • Inner cell mass
  • Trophoblast
  • Day 5 - Cavitation
  • Uterine epithelium
  • Day 7 - Implantation
  • Day 6 - Zoa hatching
  • Amniotic sac
  • Trophoectoderm
  • Chorion
  • Amnion
  • Mesoderm
  • Embryo
  • Yolk sac
  • Digestive tract
  • Umbilical cord
  • Day 14 - Mesoderm formation
  • Day 18 - Mesoderm spreads
  • Day 23 - Amniotic sac enlarges

During embryogenesis, cells exchange signals which will determine their distinct roles, affecting their survival, division, or death.

Lecture Structure

  1. General Principles of Cell Signaling
  2. Ion-Channel Coupled Receptors
  3. G-Protein Coupled Receptors
  4. Enzyme-Linked Receptors
  5. Signal Transduction - Kinases

Signal Transduction Principles

  • Signal Transduction: The process where information is converted from one form to another.
  • Cell Signaling: Involves signal reception and transmission. A signaling cell produces a molecule that is detected by a target cell through a receptor protein, which recognizes the signaling molecule and responds to it in a specific way.

Types of Signals

  • Can be transmitted over short or long distances.
  • Types of signaling molecules include:
    • Proteins
    • Peptides
    • Amino acids
    • Nucleotides
    • Steroids
    • Fatty acid derivatives
    • Gases

Types of Communication in Cell Signaling

  1. Endocrine Signaling (remote communication) - Hormones secreted by endocrine cells into the blood circulate throughout the body.

    • Example: Pancreas produces insulin, regulating glucose uptake in other cells.

  2. Paracrine Signaling (close contact) - Local mediators act in close proximity to the secreting cell and diffuse locally into the extracellular space.

    • Example: Local mediators after injury induce cell proliferation during healing.

  3. Synaptic Signaling (neuronal signaling) - Nerve cells release neurotransmitters that bind to cell receptors.

  4. Contact-Dependent Signaling - Membrane-anchored signaling molecules transmit signals through direct contact with receptor molecules on the surface of another cell. This mechanism is important for embryonic development.

Embryonic Development and Cell Signaling

  • In the embryo, the nervous system develops from epithelial cells.
  • Some cells differentiate into neurons while transmitting an inhibitory signal to neighboring cells to remain epithelial.
  • The inhibitory signal involves the signaling molecule Delta and its receptor Notch, which are both transmembrane proteins. Mutations in this signaling pathway can lead to an imbalance in cell type production.

Stages of Cell Signaling

  1. Reception: The receptor receives the signal from the extracellular fluid.
  2. Transduction: The signal is converted and relayed through the cytoplasm via relay molecules in a signaling pathway.
  3. Response: The activated cellular response occurs in response to the specific signal.
  • A cell processes hundreds of signals, selectively responding to those for which it has the corresponding receptor.

Complexity of Signal Transduction

  • The complexity depends on each target cell's unique collection of receptors.

- The same signaling molecule may induce different responses in different cells depending on their intracellular machinery or receptor type.

Receptor Activation and Signaling Pathways

  • A receptor protein activated by an extracellular signal creates an intracellular signal, which is transduced sequentially by multiple intracellular signaling molecules.
  • This leads to various cellular responses, including enzyme activation, alterations in gene expression, or changes in cytoskeletal arrangements.
Characteristics of Intracellular Signaling Cascades:
  1. Transformation: Converts the signal into a form that elicits a response.
  2. Transfer: Relays the signal to the cellular mechanism responsible for the response, often in a different cellular area.
  3. Amplification: Enhances the signal intensity (few extracellular signals can prompt a large response).
  4. Distribution: Influences multiple cellular processes through branching cascades.
  5. Regulation: Each step of the cascade is susceptible to modulation by internal or external factors.

Categories of Signaling Molecules

  1. Large or Hydrophilic Molecules: Cannot cross the membrane and must bind to transmembrane receptors.
  2. Small Hydrophobic Molecules: Can penetrate the membrane, activating enzymes or binding to intracellular receptors that regulate gene expression.
    • Example: Nitric Oxide (NO)

Nitric Oxide (NO)

  • Produced from the amino acid arginine, acting as a local mediator in tissues.
  • NO has a very transient action in the body, lasting only 5-10 seconds before converting to nitrites or nitrates.
  • Activates various intracellular signaling molecules upon entering the cell, causing relaxation of smooth muscle cells and increased blood flow.
  • Treatment Applications:
    • Nitroglycerin: Converts to NO and is effective in treating angina pectoris due to its rapid onset (2-5 minutes) and short duration (30 minutes).
    • Guanylyl Cyclase (GC): Intracellular target of NO, catalyzing the formation of cGMP from GTP, leading to vasodilation (widening of blood vessels).

PDE5 and Sildenafil (Viagra)

  • PDE5 catalyzes the conversion of cGMP to GMP in blood vessels.
  • Viagra combats male impotence by:
    1. Increasing NO production in response to nervous stimulation.
    2. Inhibiting PDE5, prolonging cGMP action.

Steroid Hormones Signaling

  • Some hormones are fat-soluble and penetrate the membrane, binding to intracellular receptors within the cytoplasm or nucleus that regulate gene expression.
  • Upon binding, receptor conformation changes, allowing the activated hormone-receptor complex to bind to specific DNA sequences, promoting or inhibiting transcription.
Example: Testosterone Signaling
  • Testosterone is converted to Dihydrotestosterone (DHT) by the enzyme 5-alpha-reductase.
  • Binding activates the androgen receptor (AR) leading to its translocation into the nucleus. The DHT-AR complex then influences gene expression related to male characteristics.

Complete Androgen Insensitivity Syndrome (CAIS)

  • Genetic males (XY chromosomes) can have mutations leading to an inability to respond to testosterone, resulting in female characteristics.
Detection of CAIS
  • Criteria include:
    1. Normal serum testosterone levels.
    2. Karyotype: person with XY sex chromosomes.
    3. Histological detection of absent testosterone receptors.
  • Detection and genetic testing are available, demonstrating >95% detectability in CAIS cases.

Gender Diversity and Identity

  • Gender identity may not align with biological sex. When one identifies and expresses differently from societal norms, they may experience gender dysphoria.
  • Terms:
    • Transgender: Individuals whose gender expression is inconsistent with their biological sex.
    • Cisgender: Individuals whose gender identity aligns with their biological sex.
  • Intersex individuals possess a combination of chromosomes and sex characteristics that do not fit the binary definitions of male and female, with prevalence rates of 1 in 100.

Legal Recognition of Gender Identity

  • Recent laws recognize an individual's right to their gender identity, upholding Personal identity, even if it contrasts with the assigned gender at birth based on biological characteristics.
  • The concept of gender identity encompasses the personal sense of one's body and its external expression, which may involve medical interventions for alignment.

Key Immunological Factors and Molecular Switches

  1. Molecular switches:
    • Classified based on how they are activated (phosphorylation vs. GTP binding).
    • Activity regulated by kinase/phosphatase or GTPase mechanisms.
  2. G-proteins are integral to signaling via G-protein-coupled receptors and modulate active/inactive states based on nucleotide binding.

Kinase Mechanisms

  • ATP is the primary donor for phosphorylation reactions, forming regulatory states that last until reversed by phosphatases.
  • GTP's unique properties allow for distinct, reversible signaling states crucial for cell signaling pathways. This separation minimizes metabolic noise and facilitates sharp molecular switches across various biological functions.