Shaebani, M. R. | Search bioRxiv

bioRxiv2024

Tau accelerates tubulin exchange in the microtubule lattice

Microtubules are cytoskeletal filaments that exhibit dynamic tip instability and, as recent discoveries reveal, possess a dynamic lattice undergoing continuous tubulin loss and incorporation. In this study, we investigate the role of tau, a neuronal microtubule-associated protein (MAP) known for its stabilizing effects on microtubules, in modulating lattice dynamics. Using in vitro reconstitution, kinetic Monte Carlo modeling, and molecular dynamics simulations, we reveal that tau, despite lacking enzymatic activity, accelerates tubulin exchange within the lattice, particularly at topological defect sites. Tau appears to stabilize longitudinal tubulin-tubulin interactions while destabilizing lateral ones, thereby enhancing the mobility and repair of lattice defects. These results challenge the traditional view of tau as merely a stabilizer, uncovering its active role in dynamically modulating microtubule lattice structure.

biophysics↗

bioRxiv2020

Vimentin provides target search efficiency and mechanical resilience for dendritic cell migration

Dendritic cells use amoeboid migration to pass through confined tissues to reach the lymph nodes, and this homing function is crucial for immune responses. The underlying mechanisms for this type of migration remain unknown. As vimentin intermediate filaments regulate adhesion-dependent migration, we analyzed whether they have a similar effect on amoeboid migration. We show that lack of vimentin impairs amoeboid migration in vitro in confined environments, and blocks lymph-node homing in mice in vivo. Importantly, we show that vimentin-deficient dendritic cells have a lower coupling factor between cell speed and persistence and reduced target search efficiency (e.g., finding a pathogen, or another cell). These data show that the characteristics of vimentin in its dynamic regulation of cell stiffness and load-bearing, and also elastic capacity, appear to explain the coupling between their migratory ability and search efficiency. Taken together, these data show that vimentin provides the specific mechano-dynamics required for dendritic cell migration and for efficient target searching. Summary statementVimentin contributes to the mechanical stiffness of cells required for amoeboid cell migration through confined spaces, and improves cell-search efficiency. Vimentin-deficient cells migrate more slowly and their migration speed is less coupled to persistence compared to control cells.

biophysics↗