LECTURE 1 NEW

Question 1

Importance of the Cytoskeleton

Answer 1

Essential for cell shape, internal organization, and functional polarity.
Involved in processes such as muscular movement, intracellular transport, embryonic development, and cancer cell migration.

Question 2

Cytoskeletal Components

Answer 2

Actin (Microfilaments): Composed of monomeric actin protein, providing structural support and facilitating cell motility.
Microtubules: Formed from α- and β-tubulin, providing structural support and aiding in cell polarity and motility.
Intermediate Filaments: Comprised of proteins like keratin, providing structural integrity to cells.

Question 3

Actin prevelence and types

Answer 3

Prevalence: Major intracellular protein in eukaryotes, especially in muscle cells (10% of total protein).
Isoforms: Six actin genes in humans with three main types based on charge:
α-actin: Involved in contractile structures.
β-actin: Found in cell cortex and motile cell edges.
γ-actin: Present in stress fibers.

Question 4

Actin Dynamics

Answer 4

Actin assembly can rapidly change; regulated by accessory proteins.
Assembly Phases: Lag, elongation, and steady state.
Critical Concentration (Cc): The minimum G-actin concentration needed for filament formation.

Question 5

Actin structure

Answer 5

G-actin: Globular monomer that assembles into filamentous F-actin.
Polarity: F-actin has a (+) end for growth and a (−) end for disassembly, with ATP binding sites oriented toward the same end.

Question 6

Actin Binding Proteins

Answer 6

Profilin: Enhances ATP exchange on G-actin, promoting filament growth.
Cofilin: Binds ADP-actin, destabilizing filaments and enhancing disassembly.
Thymosin beta-4: Sequesters G-actin to prevent assembly.

Question 7

How does Actin Assembly begin

Answer 7

The initial formation of an actin nucleus is the rate-limiting step for polymerization.

Formins and Arp2/3 complexes are key nucleating proteins that facilitate actin assembly.

Formins: Nucleate unbranched filaments, facilitating the growth of long actin structures.
Arp2/3 Complex: Nucleates branched filaments, requiring activation by nucleation-promoting factors (NPFs).

Question 8

Actin stabilization

Answer 8

Stabilization of microfilaments is achieved through capping proteins like Tropomodulin (at the (−) end) and CapZ (at the (+) end

Question 9

Cross-linking Proteins:

Answer 9

Cross-linking proteins are specialized proteins that bind to actin filaments (F-actin) and organize them into specific structure such as bundles or networks

Fimbrin: Bundles filaments with similar polarity.
Filamin: Forms stabilizing cross-links between actin filaments, creating a mesh-like network.

Question 10

Adapter Proteins

Answer 10

Adapter proteins serve as connectors between the actin cytoskeleton and other cellular components, such as membrane proteins

Spectrin: Forms networks beneath the plasma membrane, maintaining cell shape.
Dystrophin: Links actin networks in muscle cells to the extracellular matrix, essential for muscle function.

Question 11

Duchenne Muscular Dystrophy (DMD)

Answer 11

A genetic disorder due to dystrophin mutations, leading to muscle degeneration and impaired function.