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.