Zn2+ decoration of microtubules arrests axonal transport and displaces tau, doublecortin, and MAP2C

Author:

Minckley Taylor F.1ORCID,Salvagio Lyndsie A.1ORCID,Fudge Dylan H.1ORCID,Verhey Kristen2ORCID,Markus Steven M.3ORCID,Qin Yan1ORCID

Affiliation:

1. University of Denver 1 Department of Biological Sciences, , Denver, CO, USA

2. University of Michigan 3 Department of Cell and Developmental Biology, , Ann Arbor, MI, USA

3. Colorado State University 2 Department of Biochemistry and Molecular Biology, , Fort Collins, CO, USA

Abstract

Intracellular Zn2+ concentrations increase via depolarization-mediated influx or intracellular release, but the immediate effects of Zn2+ signals on neuron function are not fully understood. By simultaneous recording of cytosolic Zn2+ and organelle motility, we find that elevated Zn2+ (IC50 ≈ 5–10 nM) reduces both lysosomal and mitochondrial motility in primary rat hippocampal neurons and HeLa cells. Using live-cell confocal microscopy and in vitro single-molecule TIRF imaging, we reveal that Zn2+ inhibits activity of motor proteins (kinesin and dynein) without disrupting their microtubule binding. Instead, Zn2+ directly binds to microtubules and selectively promotes detachment of tau, DCX, and MAP2C, but not MAP1B, MAP4, MAP7, MAP9, or p150glued. Bioinformatic predictions and structural modeling show that the Zn2+ binding sites on microtubules partially overlap with the microtubule binding sites of tau, DCX, dynein, and kinesin. Our results reveal that intraneuronal Zn2+ regulates axonal transport and microtubule-based processes by interacting with microtubules.

Funder

National Institutes of Health

Publisher

Rockefeller University Press

Subject

Cell Biology

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