Biology I - Cell Biology Study Notes

Biology I-Cell Biology Lectures 2025-2026

Faculty:

  • Varvara Trachana
    Associate Professor of Medical Biology – Cell Biology
    Director of the Laboratory of Biology

Communication between Intracellular Compartments

Chapter 15 - Basic Principles of Cell Biology

Source: Alberts et al.

Protein Transport Mechanisms

Overview
  • Protein transport across cellular membranes is an essential process for maintaining cellular function and organization.
  • This transport requires energy, especially for specific transport pathways.
Mechanisms of Protein Transport

  1. Nuclear Pores - Gated Transport:

    • Transfer from the cytoplasm to the nucleus via nuclear pores.
    • This pathway is selective, allowing only certain proteins equipped with nuclear localization signals (NLS) to pass.

  2. Protein Translocators:

    • From the cytoplasm to mitochondria, peroxisomes, and the endoplasmic reticulum (ER).
    • Proteins must be unfolded (denatured) to translocate across the membranes of these organelles.

  3. Vesicular Transport:

    • From the ER to the plasma membrane (via the Golgi apparatus) and other organelles within the endomembrane system.
    • This involves the use of transport vesicles.
Goals of Protein Transport
  • Protein Sorting and Maintenance:
    • Organization of proteins within various compartments within the cell.
    • Ensures that proteins reach their specific destinations where they perform their functions.
  • Communication between Compartments:
    • Facilitated via vesicular transport:
      • Endocytosis: Intake of extracellular proteins.
      • Exocytosis: Release of proteins from the cell.

Secretory and Endocytic Pathways

Secretory Pathway (Exocytosis)
  • Process initiated in the Rough ER where proteins are synthesized.
  • After synthesis, proteins enter the ER, proceed through the Golgi system, and reach the plasma membrane.
  • Key Features:
    • Transport vesicles carry proteins from the ER to the Golgi apparatus, and from the Golgi to the cell surface.
    • Some proteins are directed towards lysosomes through endosomes.
Endocytic Pathway
  • Involves the uptake of extracellular materials into cells.
  • Materials absorbed through the plasma membrane reach endosomes, and ultimately lysosomes where digestion occurs.
  • Distinction between endocytic and secretory pathways:
    • Proteins derived from exocytosis increase membrane integrity while proteins taken in via endocytosis are later digested and reused.

Transport Vesicles Characteristics

  1. Distinct Identity:
    • Each vesicle maintains its unique protein and lipid composition.
  2. Specificity:
    • Transfers specific proteins suited for designated compartments and can only fuse with the membrane of the corresponding target organelle.
  3. Recognition Events:
    • Enabled by membrane-associated proteins on the vesicle.

Clathrin-Coated Vesicle Formation

Mechanism Overview

  • Clathrin-coated vesicles are important for endocytosis and protein transport.
  • The vesicle budding from membranes involves the following processes:
    • Formation of a clathrin-coated pit at the plasma membrane.
    • Accumulation of clathrin molecules forms a basket-like structure, enabling vesicle formation.
    • The protein dynamin encircles the neck of the budding vesicle and promotes membrane scission via GTP hydrolysis.

Adaptins in Vesicle Formation

Role of Adaptins

  • Adaptins are crucial for the selection and specificity of protein transport.
    • Types of Adaptins:
    • Adaptin 1: For transport from Golgi to lysosomes through endosomes.
    • Adaptin 2: For transport from membrane to endosomes and lysosomes.
  • Adaptins trap cargo receptors, ensuring specific proteins are selected for transport.

Motor Proteins in Vesicle Transport

  • Vesicles are often transported along cytoskeletal fibers through active transport, utilizing motor proteins such as kinesins and dyneins.
  • These motor proteins facilitate the movement of vesicles towards their target compartments, ensuring efficient delivery of cargo.

Mechanism of Vesicle Recognition and Docking

  • Vesicles possess unique molecular indicators recognized by their respective receptors on target membranes, known as SNARE proteins (vSNAREs and tSNAREs).
  • SNARE proteins facilitate the docking and fusion of vesicles with target membranes through a mechanism that brings membranes close together, promoting fusion.

SNARE Proteins Overview

  • Best-studied SNAREs: Facilitate synaptic vesicle fusion at presynaptic neurons, a critical process in neurotransmitter release.
  • SNARE proteins are targets of neurotoxins from bacteria responsible for botulism and tetanus.

Botulism

  • Caused by the toxin from Clostridium botulinum, with a mortality rate of 25% to 70%.
  • Symptoms include paralysis, with initial effects on cranial and pharyngeal muscles, leading to severe respiratory distress.
  • Urgent medical intervention with anti-botulinum serum is vital.

Tetanus

  • Tetanus is caused by Clostridium tetani, producing tetanospasmin neurotoxin.
  • Infection through injuries leads to rigid muscle spasms. Symptoms usually appear 6 to 20 days post-infection.
  • Recognized through prolonged muscle contractions and often leads to mortality if untreated.

Functional Implications of SNAREs and Neurotoxins

  • SNAREs are vital for synaptic vesicle interaction with presynaptic membranes, highlighted by interactions with botulinum and tetanus neurotoxins.
  • Botulinum neurotoxin (BoNT): Severely disrupts neuromuscular signaling, as it cleaves SNARE proteins.
  • Despite its danger, BoNT finds therapeutic uses in treatments like chronic migraines and cosmetic procedures (Botox).

Exocytosis in Cellular Function

Secretory Pathway

  • Proteins, lipids, and carbohydrates are transported from the ER to the Golgi for modification, then secreted via vesicles to the cell surface.
  • Proteins must be properly folded to be released from the membrane.
  • Post-translational modifications include:
    1. Formation of disulfide bonds for stability.
    2. Glycosylation: Protects against degradation, aids in folding, and assists in vesicle targeting.

Quality Control in the Endoplasmic Reticulum (ER)

  • Proteins must undergo strict quality control to ensure proper folding. - Chaperone proteins assist in achieving the correct structure.
  • Misfolded proteins are targeted for degradation rather than transport, emphasizing the importance of protein quality control in cellular function.
  • Example: Cystic Fibrosis (CF) arises from a mutation affecting protein folding and transport, leading to thick mucus buildup and serious health issues.

Golgi Apparatus

Structure

  • The Golgi apparatus consists of flattened membrane-bound sacs known as cisternae (3-20 per stack).
  • The entry side (cis-Golgi) receives molecules from the ER, while the exit side (trans-Golgi) directs them toward their destinations.

Processes

  • Protein Processing: Further modifications occur, including additional glycosylation.
  • Sorting: Proteins destined for either secretion or lysosomal activity are sorted based on signals they contain as they exit the trans-Golgi.

Types of Exocytosis

  1. **Constitutive Exocytosis:

    • A default pathway that does not require specific signaling.
    • Frequently delivers lipids and membrane proteins to augment membrane area.

  2. Regulated Exocytosis:

    • Occurs in specialized secretory cells (hormone-secreting) based on extracellular signals.
    • Substances are stored and only released when required (e.g., insulin release upon glucose uptake).

Pathways to Lysosomes

Lysosome Function

  • Lysosomes are membrane-bound organelles containing hydrolytic enzymes for intracellular digestion.
  • Enzymes work optimally under acidic conditions (pH~5).

Pathways Leading to Lysosomes

  • Phagocytosis: Uptake of large particles.
  • Endocytosis: Uptake of extracellular fluids or molecules.
  • Autophagy: Degradation of damaged organelles or cellular components.

Endosomes and Lysosomal Uptake

  • Endosomes serve as sorting stations where receptors recycle or transfer materials for degradation.
  • LDL Uptake: Cholesterol is bound to LDL, which is internalized through receptor-mediated endocytosis and delivered to lysosomes for hydrolysis.

Pathogen Entry via Endocytosis

  • Various pathogens exploit endocytosis to enter host cells, including HIV and coronaviruses.
  • Understanding these pathways aids in developing therapeutic and preventative measures.