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Burute, M.

Publications and source records attributed to Burute, M..

3 recordsLinked to original sources

Matrix elasticity gradients guide neuronal polarity by controlling microtubule network mobility

Neuronal polarization and axon specification depend on extracellular cues, intracellular signaling, cytoskeletal rearrangements and polarized transport, but the interplay between these processes has remained unresolved. The polarized transport of kinesin-1 into a specific neurite is an early marker for axon identity, but the mechanisms that govern neurite selection and polarized transport are unknown. We show that extracellular elasticity gradients control polarized transport and axon specification, mediated by Rho-GTPases whose local activation is necessary and sufficient for polarized transport. Selective Kinesin-1 accumulation furthermore depends on differences in microtubule network mobility between neurites and local control over this mobility is necessary and sufficient for proper polarization, as shown using optogenetic anchoring of microtubules. Together, these results explain how mechanical cues can instruct polarized transport and axon specification.

cell biology↗

A live-cell marker to visualize the dynamics of stable microtubules

The microtubule (MT) cytoskeleton underlies processes such as intracellular transport and cell division. Immunolabeling for post-translational modifications of tubulin has revealed the presence of different MT subsets, which are believed to differ in stability and function. Whereas dynamic MTs can readily be studied using live-cell plus-end markers, the dynamics of stable MTs have remained obscure due to a lack of tools to directly visualize these MTs in living cells. Here, we present a live-cell marker to visualize stable MTs and explore their dynamics. We demonstrate that a rigor mutant of kinesin-1 binds selectively to acetylated MTs without affecting MT organization and organelle transport. These MTs are long-lived, do not depolymerize upon nocadozale-treatment or laser-based severing, and display rich dynamics, including undulation, looping and sliding. This marker will help to explore how different MT subsets contribute to cellular organization and transport.

cell biology↗

Intermediate filaments control collective migration by restricting traction forces and sustaining cell-cell contacts

Mesenchymal cell migration relies on the coordinated regulation of the actin and microtubule networks which participate in polarised cell protrusion, adhesion and contraction. During collective migration, most of the traction forces are generated by the acto-myosin network linked to focal adhesions at the front of leader cells, which transmit these pulling forces to the followers. Here, using an in vitro wound healing assay to induce polarisation and collective directed migration of primary astrocytes, we show that the intermediate filament (IF) network composed of vimentin, GFAP and nestin contributes to directed collective movement by controlling the distribution of forces in the migrating cell monolayer. Together with the cytoskeletal linker plectin, these IFs control the organisation and dynamics of the acto-myosin network, promoting the actin-driven treadmilling of adherens junctions, thereby facilitating the polarisation of leader cells. Independently of their effect on adherens junctions, IFs influence the dynamics and localisation of focal adhesions and limit their mechanical coupling to the acto-myosin network. We thus conclude that IFs promote collective directed migration by restricting the generation of traction forces to the front of leader cells, preventing aberrant tractions in the followers and by contributing to the maintenance of lateral cell-cell interactions.

cell biology↗