CellBiology 3/27 lecture

  • Function of Lysosomes

    • Lysosomes are organelles that contain acid hydrolytic enzymes responsible for breaking down waste materials and cellular debris.
    • They play an essential role in degrading and recycling cellular components, which is vital for cellular homeostasis.

  • Protein Targeting to Lysosomes

    • Specific proteins destined for lysosomal degradation are tagged with a signal, typically Mannose-6-Phosphate (M6P) which ensures proper localization to lysosomes.
    • The M6P receptors facilitate the transport of acid hydrolases from the trans-Golgi network to the lysosome, preventing the escape of untagged hydrolases to the plasma membrane.

  • Transport Mechanisms

    • Clathrin-Coated Vesicles:
    • Clathrin proteins coat vesicles that transport materials between different parts of the cell, including endocytosis (internalizing materials), recycling, and degradation.
    • Different clathrin coats (AP1, AP2, AP3) associate with different membrane types and cellular activities related to the direction of transport.
    • Endocytosis:
    • A process whereby external materials (e.g., LDL) are brought into the cell through vesicle formation.
    • Involves recognition by specific receptors on the plasma membrane.
    • Phagocytosis:
    • A form of endocytosis, specifically in phagocytic cells, that engulfs large particles or microorganisms.
    • Macropinocytosis:
    • Cellular mechanism for sampling extracellular fluid along with dissolved solutes.
    • Autophagy:
    • A cellular cleanup process that degrades and recycles components through the formation of autophagosomes.
    • Can be selective (targeting specific organelles) or non-selective (degrading large areas of cytoplasm).

  • Key Cellular Diseases Connected to Lysosomal Function

    • Lysosomal Storage Diseases:
    • Genetic diseases caused by deficiency in lysosomal hydrolases.
    • Examples:
      • Tay-Sachs Disease: Mutation causing GM2 ganglioside accumulation in neurons, leading to neurodegeneration and early mortality.
      • Gaucher's Disease: A deficiency in a specific enzyme that can be treated with enzyme replacement therapy due to receptor recycling capabilities for targeting the missing enzyme to lysosomes.
      • I-Cell Disease: A severe form involving phosphotransferase mutation, leading to general lysosomal dysfunction and early life mortality.

  • Mechanism of Receptor Regulation

    • Receptors on the cell membrane can be recycled back, degraded, or relocated (transcytosis).
    • Ubiquitination:
    • Process whereby receptors can be tagged for degradation via the addition of ubiquitin molecules, guiding them towards lysosomal degradation.
    • Mono and polyubiquitination influence the fate and recognition of receptors during internalization.

  • Signaling Pathways and Autophagy Regulation

    • mTOR (mechanistic Target of Rapamycin) acts as a key regulator of cell metabolism and autophagy:
    • Activation of mTOR inhibits autophagy under nutrient-rich conditions, promoting growth and proliferation.
    • Under nutrient deprivation, pathways that activate autophagy will be promoted, allowing cells to recycle materials for survival.
    • Cytoskeletal Dynamics:
    • For processes like endocytosis and autophagy, the cytoskeletal network (actin, microtubules) is crucial for membrane movement and vesicle transport, highlighting the importance of structural proteins in cellular organization.
    • Intracellular Transport:
    • The escort machinery facilitates the invagination and processing of internalized receptors or proteins, ensuring they reach appropriate cellular destinations (lysosomes).

  • Homework Review

    • Watch animations on the dynamic processes of cytoskeleton components, such as actin and microtubules, for further understanding in upcoming lessons.