Endomembrane System and Cytoskeleton: Study Guide Notes

Endomembrane System

Types of Endoplasmic Reticulum (ER)

The endoplasmic reticulum (ER) is a key organelle in eukaryotic cells, divided into two main types: rough ER and smooth ER. Each type has distinct structures and functions.

• Rough ER:

  • Definition: The rough ER is studded with ribosomes on its cytosolic surface, giving it a 'rough' appearance.

  • Functions:

    • Protein synthesis for membrane-bound or secreted proteins.

    • Co-translational and post-translational import: Proteins are imported into the ER during or after translation. Single-pass or multi-pass integral membrane proteins have different import mechanisms, depending on the location of their N- or C-terminus.

    • Quality control: Chaperone proteins like BiP help fold proteins correctly. Misfolded proteins are either refolded or targeted for degradation.

• Smooth ER:

  • Definition: The smooth ER lacks ribosomes and appears smooth under a microscope.

  • Functions:

    • Lipid synthesis, including steroid hormones.

    • Detoxification of drugs and poisons.

    • Glycogen breakdown in liver cells.

    • Sarcoplasmic reticulum (a specialized smooth ER) stores and releases calcium ions for muscle contraction.

Example: Hepatocytes (liver cells) have abundant smooth ER for detoxification and glycogen metabolism.

Golgi Apparatus

The Golgi apparatus is a series of flattened membrane-bound sacs involved in modifying, sorting, and packaging proteins and lipids.

• Structures: Cisternae (flattened sacs), cis-Golgi network (entry), trans-Golgi network (exit).

• Functions:

  • Protein glycosylation and sorting.

  • Differences between cis and trans networks: The cis network receives vesicles from the ER, while the trans network sorts and dispatches vesicles to their final destinations.

  • Models for transport: Vesicular transport model (cargo moves via vesicles) and cisternal maturation model (cisternae themselves mature and move).

  • Difference between anterograde (ER to Golgi to plasma membrane) and retrograde (Golgi to ER) transport.

Example: Secretory cells use the Golgi to process and export hormones.

Glycosylation

Glycosylation is the process of adding carbohydrate groups to proteins and lipids, primarily occurring in the ER and Golgi apparatus.

• Steps:

  • Initial glycosylation occurs in the ER.

  • Further modification and processing in the Golgi.

  • Oligosaccharide chains are assembled and flipped to face the ER lumen.

• Importance: Glycosylation affects protein folding, stability, and cell signaling.

Example: Glycoproteins on the cell surface are critical for cell-cell recognition.

Protein Trafficking

Protein trafficking refers to the movement of proteins from their site of synthesis to their final destination within or outside the cell.

• Destination Determination: Signal sequences and tags direct proteins to specific organelles or for secretion.

• ER Retention and Retrieval: Proteins destined to remain in the ER have retention signals; others are retrieved if they escape.

Example: Lysosomal enzymes are tagged with mannose-6-phosphate in the Golgi for delivery to lysosomes.

Exocytosis and Endocytosis

Exocytosis and endocytosis are processes for moving materials out of and into the cell, respectively.

• Exocytosis: Constitutive (continuous) or regulated (in response to signals) secretion of vesicle contents.

• Endocytosis:

  • Phagocytosis: Engulfment of large particles or cells.

  • Pinocytosis: Uptake of fluids and small molecules.

  • Receptor-mediated endocytosis: Specific uptake via receptor-ligand interactions; involves clathrin-coated pits.

Example: Macrophages use phagocytosis to ingest bacteria.

Coated Vesicles and Vesicle Transport

Vesicle transport involves movement of membrane-bound vesicles between organelles, often using protein coats.

• Types of Coats:

  • Clathrin: Endocytosis and transport from Golgi to endosomes.

  • COPI: Retrograde transport (Golgi to ER).

  • COPII: Anterograde transport (ER to Golgi).

• SNARE Proteins: Mediate vesicle fusion with target membranes.

Example: Neurotransmitter release involves SNARE-mediated vesicle fusion.

Peroxisomes

Peroxisomes are small organelles involved in lipid metabolism and detoxification.

• Functions:

  • Breakdown of fatty acids via beta-oxidation.

  • Detoxification of hydrogen peroxide using catalase.

Example: Liver cells use peroxisomes to neutralize toxins.

Cytoskeleton

Overview of Cytoskeleton

The cytoskeleton is a network of protein filaments that provides structural support, facilitates movement, and organizes cellular components.

• Main Types: Microtubules, microfilaments (actin filaments), and intermediate filaments.

Microtubules

Microtubules are hollow tubes composed of tubulin proteins, essential for cell shape, transport, and division.

• Functions:

  • Maintain cell shape and polarity.

  • Serve as tracks for motor proteins (e.g., kinesin, dynein).

  • Form mitotic spindle during cell division.

• Growth and Dynamics:

  • Grow by addition of tubulin dimers at the plus end; GTP hydrolysis regulates stability.

  • Dynamic instability: Alternating phases of growth and shrinkage.

  • Catastrophe and rescue: Sudden depolymerization (catastrophe) and regrowth (rescue).

• Microtubule-Organizing Centers (MTOCs): Structures like centrosomes and basal bodies nucleate microtubule growth.

• Microtubule-Associated Proteins (MAPs): Regulate microtubule stability and interactions (e.g., Tau, TIP, MCAK).

• Drugs Affecting Microtubules: Colchicine and taxol disrupt microtubule dynamics, affecting cell division.

Example: Neurons rely on microtubules for axonal transport.

Microfilaments (Actin Filaments)

Microfilaments are thin, flexible fibers composed of actin monomers, involved in cell movement and shape changes.

• Functions:

  • Muscle contraction, cell motility, cytokinesis.

  • Support cell cortex and microvilli.

• Monomers: G-actin (globular) polymerizes to form F-actin (filamentous).

• Polarity: Filaments have distinct plus (barbed) and minus (pointed) ends, affecting growth rates.

• Drugs Affecting Microfilaments: Cytochalasin and phalloidin alter actin polymerization.

Example: White blood cells use actin filaments for amoeboid movement.

Table: Comparison of Cytoskeletal Filaments

Filament Type	Main Protein	Diameter	Main Functions
Microtubules	Tubulin	~25 nm	Cell shape, transport, mitosis
Microfilaments	Actin	~7 nm	Motility, contraction, shape
Intermediate Filaments	Various (e.g., keratin)	~10 nm	Mechanical strength

Key Equations

• Microtubule Polymerization Rate: $\text{Rate} = k_{on}[\text{Tubulin}] - k_{off}$

• ATP Hydrolysis in Actin Filaments: $\text{Actin} + \text{ATP} \rightarrow \text{Actin-ATP} \rightarrow \text{Actin-ADP} + \text{P}_i$

Additional info: Some details, such as the specific roles of MAPs and the mechanisms of vesicle coat assembly, were expanded for clarity and completeness.