Study Notes on Exam Two Overview and Actin Cytoskeleton

Class Overview

  • Last class before fall break.

  • This session will continue the discussion on actin.

Exam Two Insights

General Observations

  • Exam two is usually a drop in average performance compared to exam one.

  • Historically, exam two has shown a downward trend in scores over the past ten years.

  • The decline is attributed to:

    • Introduction of brand new material that students are unfamiliar with.

    • Exam two emphasizes the application of knowledge to answer questions.

Scoring Analysis

  • Exam one had a higher average average score due to a more favorable grading curve.

  • Exam two results showed a more uniform distribution of grades.

  • Notably, there were more A's on exam two than on exam one—this is unusual but commendable.

Advice for Improvement

  • Do not be disheartened by a single poor exam outcome.

    • There are still four exams and multiple assignments remaining, allowing for recovery in overall grades.

  • Exam performance typically improves over time as familiarity with questions and study methods improves.

  • Emphasize careful reading of exam questions.

  • Suggested method for question comprehension:

    • Simplify the question as if explaining it to a fifth grader.

Actin Cytoskeleton Focus

Introduction to Actin

  • Actin is primarily a globular protein that serves as a monomer most of the time.

  • It is highly conserved across species.

  • Actin can spontaneously polymerize when multiple actin monomers aggregate.

  • Key characteristic:

    • It binds to ATP and catalyzes ATP hydrolysis but does not require ATP hydrolysis to polymerize.

Filament Formation Mechanisms

Tip Nucleation
  • Involves the protein formin and APC dimer (actin polymerizing complement).

  • Formin acts as a dimer and binds to APC to facilitate the assembly of actin monomers.

  • Mechanism involves the following steps:

    • Formin binds to APC and then recruits actin monomers bound to profilin.

    • This binding promotes the alignment necessary for actin filaments to grow.

  • The final filament has two distinct forms of actin based on if it is bound to ATP or ADP (older parts).

Arp2/3 Mediated Nucleation
  • Arp2/3 is a complex of several proteins that initiates filament branching.

  • Binds laterally to existing filaments to catalyze the addition of new actin monomers and forms branches.

  • Requires nucleation promotion factors to assist in recruiting ATP-bound actin to Arp2/3.

Actin Structures in Cells

Lamellipodia
  • Highly branched actin structures at the leading edge of the cell involved in cell movement.

  • Analogous to a fist forming that pushes against the plasma membrane, enabling cell movement.

  • Formed mainly through Arp2/3 and nucleation promotion factors.

Filopodia
  • Parallel bundles of actin filaments that extend from lamellipodia.

  • Less forceful than lamellipodia; act as sensory structures.

  • Involves both formin and capping proteins for their regulation.

Stress Fibers
  • Composed of anti-parallel actin bundles linked by myosin motor proteins.

  • Function to enable cell movement and structural support in various cellular functions.

Cortex
  • Composed of short, densely packed actin filaments providing structural integrity under the plasma membrane.

  • Highly cross-linked with no branching.

  • Maintains integrity and mediates interactions between the cell membrane and the cytoskeleton.

Actin Dynamics

Assembly and Disassembly
  • Rapid assembly allows for efficient cell movement through structures like lamellipodia and filopodia.

  • Disassembly is crucial for remodeling and reorganizing the actin cytoskeleton.

  • Regulated by ADF (Actin-depolymerizing factor) cofilin, which cleaves actin filaments.

Severing Mechanism
  • ADF cofilin binds to ADP-bound actin, causing structural distortion that weakens interactions and facilitates filament disassembly.

Applications and Implications

Disease Relevance

  • Actin's role in pathogen movement within host cells, utilizing the cytoskeletal framework.

  • In cancer metastasis, invadopodia facilitate the invasion of adjacent cells, spreading malignancy through the use of actin.

  • Alzheimer's disease has been linked to actin dynamics, particularly through the activity of cofilin and its interaction with tau proteins, indicating a connection between different cytoskeletal components contributing to neurodegeneration.

Summary and Takeaway Points

  • This session emphasized the importance of understanding actin dynamics for cellular movements.

  • Recognized the connections between actin dynamics, disease processes, and cellular behavior.

Conclusion

  • Open floor for questions regarding lecture content and preparation for the upcoming exam after the fall break.