BIOL112-lecture4-CW2024_48820cca13286821c3035022aac403c4

Lancaster University BIOL112 Lecture 4: The Endomembrane System

Define the endomembrane system.
Describe the structure and roles of the smooth endoplasmic reticulum (SER) including the sarcoplasmic reticulum.
Describe the structure and roles of the rough endoplasmic reticulum (RER).
Describe the structure and roles of the Golgi apparatus.
Describe the structure and roles of the lysosomal system.
Describe the processes of endo and exocytosis and understand their roles in the cell.

The endomembrane system is unique to eukaryotic cells and plays a crucial role in the synthesis, modification, and transport of proteins and lipids. It is composed of:
- Nuclear membrane
- Endoplasmic reticulum: Smooth ER (SER) and Rough ER (RER).
- Golgi apparatus
- Lysosomes

The SER is less abundant in most cell types compared to the RER and plays various important roles:
- Lipid Synthesis: It is responsible for the manufacturing of phospholipids and cholesterol, which are essential for cellular membrane structure.
- Hormone Production: In steroidogenic tissues, the SER synthesizes lipophilic hormones such as testosterone and estrogen.
- Carbohydrate Metabolism: In hepatocytes, the SER helps in breaking down glycogen into glucose, releasing it into the bloodstream when needed.
- Detoxification: It aids in detoxifying lipid-soluble drugs and poisons; enzymes in the SER add water-soluble groups (sulphate or glycuronic acid) to facilitate their excretion.

The RER is characterized by ribosomes attached to its cytosolic surface, which gives it a rough appearance:
- Protein Synthesis: It is the main site for synthesizing secreted proteins, glycosylated proteins, lysosomal enzymes, and membrane-bound proteins.
- Protein Folding: The RER provides an environment for the folding and post-translational modification of proteins, ensuring they attain their functional conformations before transportation.
- Quality Control: Misfolded proteins are recognized and retained in the ER for refolding or degradation, helping to maintain protein integrity within the cell.

Found specifically in muscle cells, it is a specialized form of the SER that is involved in muscle contraction:
- Structure: Composed of a network of tubular sacs surrounding myofibrils, facilitating rapid calcium ion transport.
- Functions: It sequesters calcium ions, which are essential for initiating contraction in muscle fibers. During muscle activation, calcium ions are released to trigger muscle contraction by enabling the interaction between myosin and actin filaments.

Muscle fibers contain myofibrils made up of repetitive units called sarcomeres, composed of thick (myosin) and thin (actin) filaments:
- Action Potentials: Received through T tubules, these lead to the release of calcium ions from the sarcoplasmic reticulum.
- Troponin and Tropomyosin: Calcium binding to troponin causes a conformational change that exposes binding sites on actin, allowing cross-bridge formation with myosin, leading to contraction.

The Golgi apparatus is essential for the processing and sorting of proteins synthesized in the RER:
- Protein Modification: It modifies proteins (e.g. glycosylation) and sorts them for transport to their final destinations, such as the plasma membrane, lysosomes, or for secretion.
- Mannose-6-Phosphate Tagging: Lysosomal enzymes are tagged with mannose-6-phosphate in the Golgi to direct them to lysosomes for degradation of cellular debris.

Lysosomes are membrane-bound organelles containing approximately 60 different hydrolytic enzymes active at acidic pH, responsible for degradation and recycling:
- Autophagy: Degrading and recycling worn-out organelles and macromolecules to maintain cellular homeostasis.
- Phagocytosis: Engulfing and digesting pathogens, cellular debris, and foreign particles, facilitating immune responses.
- Autolysis: Programmed cell death (apoptosis) involves lysosomal enzymes breaking down the cell components to ensure tidy elimination without inflammation.

These diseases arise from defects in lysosomal enzymes leading to the accumulation of undegraded materials:
- Example: Tay-Sachs disease, which involves a deficiency in the hexosaminidase A enzyme, causing ganglioside accumulation in nerve cells, typically resulting in severe neurological damage and is usually fatal by ages 2-3.

This process involves the fusion of intracellular vesicles with the plasma membrane to release their contents outside the cell, such as hormones and neurotransmitters crucial for cell signaling.

Different types of endocytosis facilitate the uptake of materials:
- Phagocytosis: The engulfing of large particles (e.g., bacteria) by immune cells like macrophages.
- Pinocytosis: A non-specific form of endocytosis where cells take in extracellular fluid and solutes.
- Receptor-Mediated Endocytosis: A specific process triggered by the binding of ligands to receptors on the cellular surface, allowing for selective uptake of molecules.

Clathrin-Coated Vesicles: These structures form during receptor-mediated endocytosis, helping to shape the vesicles and capture cargo molecules.
SARS-CoV-2 Entry: The virus utilizes receptor-mediated endocytosis to enter host cells, illustrating the importance of this mechanism in viral infections and potential therapeutic targets for treatment.