Microfilaments

The session marks the last class before fall break, with topics including exam performance and the actin cytoskeleton.

Class averages for exam two typically decline compared to exam one.
- This has been a consistent pattern observed over the past ten years.
- Reasons for decline:
- Exam II covers mostly brand new material that students are unfamiliar with.
- It emphasizes application of knowledge rather than mere recall.
Exam I saw favorable grading patterns, indicating it may have had a better curve; more students received higher grades on exam II than exam I, which is unusual.
Advice for Students:
- Do not let one poor exam grade discourage you; it is just one exam among others.
- You can improve as you become familiar with exam formats and studying techniques.
- Read questions carefully; misinterpretation is a common issue.
- Students are encouraged to explain questions in simpler terms to aid understanding.

Actin is a globular protein (G-actin) that can assemble into microfilaments (F-actin).
Highly conserved across species.
Spontaneous growth can occur when multiple actin monomers bind together; ATP is required but does not need to be hydrolyzed for filament formation.

Tip Nucleation
- Involves formin protein which helps nucleate the formation of actin filaments.
- Forming functionally acts as an anchor, encouraging actin monomers to come together.
- Needs ATP-bound actin to facilitate this process.
- Profilin protein inhibits spontaneous actin filament formation by binding to actin monomers; its release allows polymerization to proceed.
- Each actin bound with ATP is colored yellow in the graphical representation, indicating that the protein is ready to polymerize.
ARP2/3-mediated Nucleation
- The ARP2/3 complex initiates branched filament growth from the sides of pre-existing filaments.
- Primarily responsible for creating branched structures like lamellipodia.
- Requires nucleation promoting factors (NPFs) to assist in the process of branching and growth.
- Upon bonding to the actin filament, ARP2/3 becomes stationary and cannot slide like formin.

Highly branched structures facilitating cell movement.
Comprised primarily of branched actin filaments.
Characterized by high density and rapid formation, providing significant pushing force against cell membranes.
Growth is mediated through the actions of ARP2/3 and associated NPFs while capping proteins limit growth length.
Example: When formed, they can create a strong force, comparable to having a fist that punches against a wall (representative of the plasma membrane).

Thin, rod-like protrusions that emerge from lamellipodia; less forceful than lamellipodia.
Comprised of parallel actin bundles, formed with the assistance of formin and stabilized by anti-capping proteins.
Serves sensory roles for the cell, with receptors to probe the environment.

Composed of anti-parallel arrays of actin; they provide support and shape to the plasma membrane.
Myosin, a motor protein, interacts with these actin structures and is instrumental in contractions and movements.
Forms either parallel (moving the cell forward) or anti-parallel configurations, associated with flexible cellular movements.

A dense network of short actin filaments located just beneath the plasma membrane.
Highly cross-linked ensuring mechanical stability; does not utilize ARP2/3 for branching, instead relies on formin for nucleation.
Contributes to cell shape and resistance, protecting membranes.

Actin structures are not static; they can be rapidly built and disassembled.
Severing Dynamics: ADF-cofilin protein binds to ADP-actin regions and alters filament stability, causing deformation that weakens structural integrity, leading to potential collapse under pressure.
ADF-cofilin’s effect depends on its concentration in a localized region:
- Low concentrations: Rapid severing of actin.
- High concentrations: Slower severing of actin structures, promoting flexibility rather than immediate breakdown.
Example: Comparing flexibility in lumber cuts to understand severing dynamics in a practical context.

Actin structures play vital roles in pathologies, especially in cancer and neurodegeneration.
- Invadopodia: Cellular protrusions that facilitate cancerous cell invasion into surrounding tissues, responsible for cell metastasis.
- Study findings regarding Alzheimer's disease demonstrate co-localization of actin degradation (via cofilin) and tau protein aggregates, indicating interdependencies between actin and tubulin structures in disease states.

This lecture provided insights into actin dynamics, structures, and their systemic roles in cell functionality and pathology.
Students are reminded to continue diligent study habits leading up to exams and to remain proactive in understanding course material.
Next Steps: Review actin structure functionalities in detail and prepare for upcoming topics related to the tubulin cytoskeleton and motor proteins.

Reminder: Don't give up! The course content will become easier as you continue to engage with the material and exam formats during your studies.