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.