26.17:
Disassembly of Intermediate Filaments
The assembly and disassembly of intermediate filaments are regulated by post-translational modifications, most commonly phosphorylation by kinases and dephosphorylation by phosphatases.
Site-specific phosphorylation at the N-terminal head domain alters the conformation of the intermediate filaments to promote disassembly of preformed filaments, and prevent further assembly.
Additionally, because intermediate filaments are packed in a dense cytoskeletal mesh, kinases in close proximity cross-activates each other, increasing intermediate filament phosphorylation, triggering their disassembly.
During mitosis, two types of intermediate filaments, vimentin and nuclear lamins, help break down the nuclear membrane.
These intermediate filaments are phosphorylated on specific serines on the N-terminal head domain in vimentin and on either side of the central rod domain in lamins.
These post-translational modifications trigger the disassembly of intermediate filaments, resulting in the disintegration of the nuclear membrane.
The depolymerized lamin dimers remain anchored to the fragmented nuclear membrane through the covalent attachment of prenyl groups. As the cell cycle progresses into telophase, dephosphorylation of lamins allows nuclear envelope reassembly in the daughter cells.
26.17:
Disassembly of Intermediate Filaments
Intermediate filaments (IFs) do not undergo spontaneous disassembly. Enzymes, kinases, and phosphatases add and remove phosphates from specific sites to regulate their disassembly. The IF concentration in the cytoplasm also regulates the disassembly. If the concentration crosses a threshold, it activates the protein kinases in the vicinity, allowing the phosphorylation of IFs.
Keratin proteins, found at the cell periphery near cell junctions, undergo a cycle of assembly and disassembly. In Type III and IV intermediate filaments, the phosphorylation of the N-terminal head domain by the secondary messenger-dependent kinase proteins influences the phosphorylation of the C-terminal tail, that aids in their disassembly.
During mitosis, the transition from prophase to pro-phase results in the nuclear lamins, vimentin, and glial fibrillary acidic proteins undergoing site-specific phosphorylation by Rho kinase, Cdk1, Aurora-B, and PAK1, resulting in disassembly. The phosphorylation of lamins A, B, and C leads to depolymerization of the filaments into lamin dimers, further leading to nuclear membrane disintegration. The lamins remain attached to the disintegrated membrane through their C-terminal prenylation. The removal of phosphates through phosphatase leads to the reassembly of the lamin meshwork during the telophase.
Suggested Reading
- Sihag, R.K., Inagaki, M., Yamaguchi, T., Shea, T.B. and Pant, H.C., 2007. Role of phosphorylation on the structural dynamics and function of types III and IV intermediate filaments. Experimental cell research, 313(10), pp.2098-2109.
- Kölsch, A., Windoffer, R., Würflinger, T., Aach, T. and Leube, R.E., 2010. The keratin-filament cycle of assembly and disassembly. Journal of cell science, 123(13), pp.2266-2272.