The Cytoskeleton Overview

The Cytoskeleton

• Cells require organization in space and interaction with their environment for proper function.
• Cells need a correct shape, structural integrity, and the ability to change shape and move.
• Internal components need to be rearranged as needed (growth, division, adaptation).
• The cytoskeleton, a system of filaments, facilitates these spatial and mechanical functions.

Types of Protein Filaments

• The cytoskeleton's function depends on three main filament families: actin filaments, microtubules, and intermediate filaments.
• Each filament type has distinct mechanical/biological properties and roles, but all share fundamental features.
• These filaments work together to provide strength, shape, and movement capabilities to the cell.

Actin Filaments

• Actin filaments, also known as microfilaments, are helical polymers of the protein actin.
• They have a diameter of 8 nm and can form linear bundles, networks, and gels.
• Actin filaments are highly concentrated in the cell cortex (just beneath the plasma membrane).
• They are involved in cell surface projections (microvilli, filopodia, lamellipodia, and pseudopodia).
• They contribute to cell movement and exploration of its environment.

Microtubules

• Microtubules are long, hollow cylinders (25 nm diameter) made of the protein tubulin.
• They are rigid and straight, frequently attached to a microtubule-organizing center (MTOC) called a centrosome.
• Microtubules play roles in organelle positioning, intracellular transport, and forming the mitotic spindle during cell division.
• Cilia and flagella are also composed of microtubules.

Intermediate Filaments

• Intermediate filaments are rope-like fibers (10 nm diameter) composed of a large family of intermediate filament proteins.
• They form a meshwork within the nucleus (called the nuclear lamina).
• They can span across the cytoplasm providing mechanical strength to cells.
• They can form strong linkages between cells (e.g., skin/epithelium).

Cytoskeletal Filaments: Dynamic Structures

• Large-scale cytoskeletal structures can change or persist according to a cell's needs.
• Macromolecular components of these structures are in a constant state of flux.
• Rearrangement within a cell requires little energy when conditions change.

Cell Division and the Cytoskeleton

• Cells reorganize actin and microtubule filaments during division.
• Actin filaments form contractile rings pinching the cell in two during cytokinesis.
• Microtubule arrays are reorganized into a spindle to separate chromosomes.

Nucleus and Cytoskeleton Interactions

• The nuclear lamina, a meshwork of intermediate filaments, is located just beneath the inner nuclear membrane.
• This structure adds strength and stability to the nucleus.

Nucleation (Rate Limiting Step in Actin Filament Formation)

• Actin subunit assembly into filaments is regulated by nucleation, which is the formation of an initial oligomer or nucleus of subunits.
• The stable nucleus then rapidly elongates by adding more subunits.
• Nucleation is rate limiting, as this initial step determines the overall polymerization rate.

Polymerization On/Off Rates & Critical Concentration (Cc or Kd)

• Subunits are added to and removed from the filament ends at specific rates (kon and koff).
• The rate of addition is proportional to the free subunit concentration (konC).
• Subunits' removal rate is constant (koff) and independent of free subunit concentration.
• Equilibrium occurs when the addition and loss rates are equal, at a constant Critical Concentration.

The Critical Concentration (Cc)

• The critical concentration (Cc or Kd) is the concentration of free subunits at which the rate of subunit addition equals the rate of subunit loss.
• The polymerization of a polymer stops when the concentration of free monomers reaches this critical level.

Time Course of Polymerization

• Polymerization of filaments like actin or microtubules follows a three-phase pattern.
  • Lag phase: characterized by initial nucleation steps.
  • Growth phase: filaments elongate rapidly.
  • Equilibrium phase: rates of addition and loss balance each other.

Plus and Minus Ends

• Filament ends grow at different rates (plus end grows faster than minus end).
• The different rates at which filaments grow on different ends are due to the conformational change of subunits as they enter polymers.

Nucleotide Hydrolysis

• ATP (or GTP) hydrolysis occurs in actin (or tubulin) filaments after monomers associate.
• This process affects filament stability and growth rates.

Accessory Proteins and Motors

• Accessory proteins regulate the length, structure, number, and attachments of filaments and their interactions within the cell.
• These proteins convert information from signaling pathways to cytoskeletal functions enabling various cellular processes including motion.

Explore the significance of the cytoskeleton in cellular structure and function. This quiz covers the types of protein filaments, including actin filaments, microtubules, and intermediate filaments, as well as their roles in maintaining cell shape and movement. Test your knowledge of how these components interact to enable cellular processes.