Question 1

How do phosphorylation and dephosphorylation regulate intermediate filament disassembly?

Accepted Answer

Phosphorylation by kinases at specific sites on the N-terminal head domain alters intermediate filament conformation, promoting disassembly and preventing further assembly. Kinases in close proximity cross-activate each other, increasing phosphorylation rates. During telophase, phosphatases remove phosphates from lamins, allowing nuclear envelope reassembly in daughter cells.

Question 2

What role do vimentin and nuclear lamins play during mitosis?

Accepted Answer

Vimentin and nuclear lamins are phosphorylated at specific serines during mitosis, triggering their disassembly and causing nuclear membrane breakdown. Lamin dimers remain anchored to fragmented nuclear membranes through prenyl group attachments. This phosphorylation is catalyzed by kinases including Rho kinase, Cdk1, Aurora-B, and PAK1.

Question 3

How does intermediate filament concentration affect their disassembly?

Accepted Answer

When intermediate filament concentration exceeds a threshold in the cytoplasm, it activates nearby protein kinases. This kinase activation increases phosphorylation of intermediate filaments, triggering their disassembly and remodeling of the dense cytoskeletal mesh. The concentration-dependent mechanism ensures coordinated regulation across the cell.

Question 4

What happens to lamins after they disassemble during mitosis?

Accepted Answer

Depolymerized lamin dimers remain covalently attached to fragmented nuclear membranes through prenylation at their C-terminal ends. As the cell cycle progresses into telophase, phosphatases dephosphorylate the lamins, allowing them to reassemble into a meshwork and reform the nuclear envelope in daughter cells.

Question 5

How do secondary messenger-dependent kinases influence Type III and IV intermediate filament disassembly?

Accepted Answer

Secondary messenger-dependent kinase proteins phosphorylate the N-terminal head domain of Type III and IV intermediate filaments. This phosphorylation influences subsequent phosphorylation of the C-terminal tail, which aids in their disassembly. This sequential phosphorylation mechanism allows coordinated regulation of these filament types.

Question 6

Why do keratin proteins undergo cycles of assembly and disassembly?

Accepted Answer

Keratin proteins, located at the cell periphery near cell junctions, undergo assembly and disassembly cycles regulated by phosphorylation and dephosphorylation. These cycles allow dynamic remodeling of the cytoskeletal network in response to cellular signals and mechanical stress at cell-cell contacts.

Question 7

How does the structure of intermediate filaments determine where disassembly occurs?

Accepted Answer

The structure of intermediate filaments, with distinct N-terminal head and C-terminal tail domains, determines where kinases and phosphatases act. Site-specific phosphorylation at these structural domains alters filament conformation, triggering disassembly. Understanding the structure of intermediate filaments explains how post-translational modifications regulate filament stability.

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