Biophysical Society Thematic Meeting | Bucharest 2026

Biophysics of Membrane Reactions in Brian

Wednesday Speaker Abstracts

WRITING AND READING THE MICROTUBULE LATTICE: BIOPHYSICAL MECHANISMS OF CELLULAR ARCHITECTURAL ORGANIZATION Tomohiro Shima The University of Tokyo, Department of Biological Sciences, Tokyo, Japan In the complex environment of the brain, maintaining a highly polarized neuronal architecture and efficient intracellular transport is essential for nervous system function. Microtubules (MTs) serve as the primary tracks for this transport, yet they constantly undergo a dynamic "scrap-and build" cycle through tubulin polymerization and depolymerization. While the precise regulation of this cycle is crucial for establishing neuronal architecture, the molecular mechanisms governing this switch have remained elusive. To address this, we combined X-ray fiber diffraction, cryo-EM, and fluorescence microscopy to investigate the structural transitions induced in the MT lattice upon the binding of regulatory proteins. Our results demonstrate that the MT lattice can adopt at least two distinct conformations: expanded and compacted lattices. We found that Kinesin-1 and CAMSAP3, both of which localize to the axon, not only preferentially bind to the expanded lattice but also actively induce a structural shift toward this state. This creates a positive feedback loop where these proteins "read" the expanded state and subsequently "write" it into the nearby lattice. Because lattice expansion inhibits depolymerization, this "read-and-write" mechanism significantly stabilizes the MTs and makes them more favorable substrates for these binding proteins. Given that axon formation requires long, stable MTs, the regulation of lattice dynamics through this "writing" mechanism likely dictates overall cellular architecture. These findings reveal a sophisticated biophysical layer of regulation where the structural plasticity of the microtubule enables the precise spatial organization and polarized transport essential for brain development and function.

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