Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Zinc Differentially Modulates the Assembly of Soluble and Polymerized Vimentin

Version 1 : Received: 9 March 2020 / Approved: 10 March 2020 / Online: 10 March 2020 (11:07:05 CET)

A peer-reviewed article of this Preprint also exists.

Mónico, A.; Zorrilla, S.; Rivas, G.; Pérez-Sala, D. Zinc Differentially Modulates the Assembly of Soluble and Polymerized Vimentin. Int. J. Mol. Sci. 2020, 21, 2426. Mónico, A.; Zorrilla, S.; Rivas, G.; Pérez-Sala, D. Zinc Differentially Modulates the Assembly of Soluble and Polymerized Vimentin. Int. J. Mol. Sci. 2020, 21, 2426.

Journal reference: Int. J. Mol. Sci. 2020, 21, 2426
DOI: 10.3390/ijms21072426

Abstract

The intermediate filament protein vimentin constitutes a critical sensor for electrophilic and oxidative stress. We previously showed that vimentin interacts with zinc, which affects its assembly and redox sensing. Here we have used vimentin wt and C328S, an oxidation-resistant mutant showing improved NaCl-induced polymerization, to assess the impact of zinc on soluble and polymerized vimentin by light scattering and electron microscopy. Zinc acts as a switch, reversibly inducing the formation of vimentin oligomeric species. High zinc concentrations elicit optically-detectable vimentin structures with a characteristic morphology depending on the support. These effects also occur in vimentin C328S, but are not mimicked by magnesium. Treatment of vimentin with micromolar zinc induces fibril-like particles that do not assemble into filaments, but form aggregates upon subsequent addition of NaCl. In contrast, when added to NaCl-polymerized vimentin, zinc increases the diameter or induces lateral association of vimentin wt filaments. Remarkably, these effects are absent or attenuated in vimentin C328S filaments. Therefore, the zinc-vimentin interaction depends on the chemical environment and on the assembly state of the protein, leading to atypical polymerization of soluble vimentin, likely through electrostatic interactions, or to broadening and lateral association of preformed filaments through mechanisms requiring the cysteine residue. Thus, impact of zinc on vimentin assembly and redox regulation is envisaged.

Subject Areas

vimentin; zinc; cysteine; redox sensing; intermediate filaments; cysteine mutant; filament bundling; filament width; divalent cations; magnesium

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