KN

Unit 08 Pt4

Basal Lamina

  • Definition: A special type of extracellular matrix associated with epidermal cells. Forms a thin, flexible fibrous mat on the basolateral side of cells.
  • Composition: Made of proteins and polysaccharides secreted locally by adjacent cells, typically 40-100 nanometers thick.
  • Location: Found beneath epithelial cells and around muscle and fat cells.
  • Functions:
    • Structural Integrity: Provides support to cells.
    • Filtration: Particularly important in the kidney glomerulus.
    • Determining Cell Polarity: Influences the orientation and functioning of cells.
    • Organizing Proteins: Arranges proteins in the plasma membrane.
    • Cell Survival, Proliferation, and Differentiation: Affects how cells grow and specialize.
    • Highway for Cell Migration: Serves as a pathway for cells that need to move through tissues.
    • Mechanical Role: Provides rigidity and structure.
  • Pathological Association: Mutations can lead to epidermolysis bullosa.

Components of Basal Lamina

  • Laminin: A flexible heterotrimeric protein that binds many components of the basal lamina and connects collagen networks.
    • Binding Domains: Includes domains for binding to type IV collagen, nidogen, and perlecan.

Extracellular Matrix (ECM)

  • Role in Repair: Rapid degradation is vital for tissue repair, ensuring old proteins are continually replaced.
    • Continuous Turnover: The ECM is constantly being remodeled, especially evident in bone tissues.
  • Cell Movement: Cells must navigate through the ECM; important for growth and immune responses.
    • Degradation: Occurs via extracellular proteases, primarily matrix metalloproteases (MMPs) and serine proteases.
    • Specificity: Some MMPs are highly specific; regulated through local activation and enzyme confinement via cell surface receptors.

Cell Interaction with ECM

  • Matrix Receptors: Transmembrane proteins (integrins) link the ECM to the cytoskeleton, essential for signaling and cellular responses.
    • Integrins: Over 24 types in humans, forming heterodimers that bind to specific ECM motifs (e.g., RGD domain in fibronectin).
    • Dynamic Adhesion: Integrins can undergo conformational changes for attachment regulation (active vs. inactive forms).
  • Inside-Out/Outside-In Activation:
    • Inside-Out Activation: Triggered by intracellular signals affecting integrin conformation.
    • Outside-In Activation: Signals from ECM that trigger changes inside the cell.
  • Cell Survival: Many cells require integrin binding to ECM to survive, which is termed anchorage dependence. Detachment can lead to apoptosis.

Signaling Mechanisms

  • Focal Adhesion Kinase (FAK): A specific kinase involved in ECM signaling, associated with focal adhesions, activating downstream signaling cascades.
  • Integrins in Pathologies: Defects in integrin functions linked to various diseases, such as muscular dystrophies and immune disorders.
  • Membrane Ruffling: Facilitated by lamellipodia, contributing to cell movement and invasive behavior in contexts like cancer and infections.