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

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

Changes in zinc levels have been observed in neuronal cells and have the potential to alter intraneuronal signaling; however, the precise mechanisms by which they elicit downstream effects have not been elucidated.  Recent work by Minckley T. et al. identified Tubulin as an important target for zinc in the regulation of neuronal function.  Preliminary live cell imaging studies were used to show that increased zinc levels resulted in a measurable reduction in both lysosome and mitochondria motility. As the transport of these organelles is facilitated by kinesins, the group examined whether zinc affected these motor proteins.  Indeed, they found that zinc directly inhibits KIF5A kinesin motility which they determined using an inducible cargo trafficking assay.  Further analysis revealed that while the movement of the kinesins was diminished with zinc, the decrease in motility was not caused by catastrophic destabilization of microtubules or detachment of KIF5A from microtubules.  These findings were supported by in vitro TIRF assays assessing the interactions of microtubules and kinesins in the presence of zinc. The group then utilized a titration of zinc to access KIF5A ATPase activity and found that picomolar levels of zinc promoted activity; however, once zinc reached nanomolar levels ATPase activity was reduced.  This led to the finding that at higher levels the zinc molecules will directly interact with microtubules and can even promote microtubule polymerization.   The bound zinc can influence interactions between microtubules and some MAPs like tau and doublecortin.  These findings suggest that zinc may have important regulatory functions in microtubule regulation, motor function, and organelle transport in neuronal cells. Cytoskeleton Inc purified KIF5A protein (Cat. # KR01) was essential for investigating how zinc controls motor proteins and axonal transport.