KN

Unit 08 Pt4

Basal Lamina Overview

  • Definition: The basal lamina is a specialized type of extracellular matrix associated with epidermal cells, forming a flexible fibrous mat on the basolateral side of cells.
  • Composition: Made up of proteins and polysaccharides secreted locally by nearby cells.
  • Thickness: Ranges from 40 to 100 nanometers.

Functions of Basal Lamina

  • Location: Found beneath epithelial cells, around muscle cells, and fat cells.
  • Separation: It separates epithelial cells from surrounding connective tissue.
  • Kidney Glomerulus: Highly abundant here and plays critical roles in filtration and structural integrity.
  • Cell Function:
    • Determines cell polarity.
    • Influences cell metabolism.
    • Organizes proteins in adjacent plasma membranes.
    • Affects processes like cell survival, proliferation, differentiation, and migration.
  • Mechanics: Has a mechanical role, and mutations can lead to conditions like epidermolysis bullosa.

Components of Basal Lamina

  • Laminin:
    • A flexible heterotrimeric protein that self-associates in vitro.
    • Binds various components of the basal lamina, linking laminin with type IV collagen, nidogen, and perlecan.

Diverse Functions

  • Molecular Filter: Acts as a filter, especially in the kidneys.
  • Barrier Function: Prevents fibroblast contact with the epithelium while permitting lymphocytes and macrophages to reach the epithelial layer.
  • Tissue Regeneration: Survives injury, providing a scaffold for cell migration during repair (e.g., neuromuscular junction).
  • Extracellular Matrix (ECM) Turnover:
    • Importance of rapid degradation for tissue repair.
    • Continuous turnover is critical for maintaining healthy ECM.

Degradation of ECM

  • Proteases Involved:
    • Matrix Metalloproteases (MMPs): Depend on calcium and zinc.
    • Serine Proteases: Reactive with serine; work closely with the cells producing them.
  • Regulation: Must be carefully controlled to target degradation accurately and involve cell surface receptors and inhibitory molecules.

Signal Transduction and ECM

  • Matrix Receptors:
    • Serve as links between the ECM and the cytoskeleton, important for regulating ECM synthesis and degradation.
    • Integrins are the principal matrix receptors:
    • Anchor cells to the ECM and transduce signals from outside to inside the cell.
    • More than 24 types in humans; play roles in various diseases.

Integrins in Cell Adhesion

  • Structure: Composed of alpha and beta subunits forming heterodimers.
  • Cellular Role:
    • Bind to specific ECM motifs (e.g., RGD domain in fibrinogen).
    • Interaction with the cytoskeleton is crucial for maintaining cell attachment and shape.
  • Hemidesmosomes:
    • Key integrin connections to laminin and keratin via accessory proteins (plectin, dystonin).

Dynamic Nature of Integrins

  • Activation: Can undergo conformational changes, allowing dynamic adhesion essential for cell responses.
  • Inside-out Activation: Triggered by intracellular signals (e.g., PIPs activating talin).
  • Pathological Implications: Defects in integrins related to various diseases like muscular dystrophies and immune disorders.

Focal Adhesions and Cell Behavior

  • Focal Adhesions: Dense plaques formed by clustered integrins; essential for transmitting mechanical and signaling forces.
  • Anchorage Dependence: Many cells require ECM attachment for survival, loss of which leads to apoptosis.
  • Integrin Signaling: Mediates cell proliferation and survival, integral for cancer metastasis.

Conclusion

  • Membrane Ruffling and Lamellipodia:
    • Membrane behavior studied in cell adhesion and invasion assays, particularly in cancer research.
  • Final Notes:
    • This concludes the course content for the term.
    • Review materials for the final exam will be posted later.