The Romet-Lemonne/Jégou Lab published a new publication in PNAS:
Continuous self-repair protects vimentin intermediate filaments from fragmentation
Abstract:
Intermediate filaments are key regulators of cell mechanics. Vimentin, a type of intermediate filament expressed in mesenchymal cells and involved in migration, forms a dense network in the cytoplasm that is constantly remodeling through filament transport, elongation/shortening, and subunit exchange. While it is known that filament elongation involves end-to-end annealing, the reverse process of filament shortening by fragmentation remains unclear. Here, we use a combination of in vitro reconstitution, probed by fluorescence imaging and atomic force microscopy, with theoretical modeling to uncover the molecular mechanism involved in filament breakage. We first show that vimentin filaments are composed of two populations of subunits, half of which are exchangeable and half immobile. We also show that the exchangeable subunits are tetramers. Furthermore, we reveal a mechanism of continuous filament self-repair, where a soluble pool of vimentin tetramers in equilibrium with the filaments is essential to maintain filament integrity. Filaments break due to local fluctuations in the number of tetramers per cross-section, induced by the constant subunit exchange. We determine that a filament tends to break if approximately four tetramers are removed from the same filament cross-section. Finally, we analyze the dynamics of association/dissociation and fragmentation to estimate the binding energy of a tetramer to a complete versus a partially disassembled filament. Our results provide a comprehensive description of vimentin turnover and reveal the link between subunit exchange and fragmentation.
Tran QD, Lenz M, Lamour G, Paty L, Varela-Salgado M, Campillo C, Wioland H, Jegou A, Romet-Lemonne G, Leduc C. Continuous self-repair protects vimentin intermediate filaments from fragmentation. Proc Natl Acad Sci U S A. 2025 Jun 17;122(24):e2417660122. doi: 10.1073/pnas.2417660122. Epub 2025 Jun 13. PMID: 40512788; PMCID: PMC12184399.