Metals in the neuronal cytoskeleton: insights from super resolution and synchrotron X-ray imaging
Zinc and copper are involved in neuronal differentiation and synaptic plasticity but the molecular mechanisms behind these processes are still elusive due in part to the difficulty of imaging trace metals together with proteins at the synaptic level. We correlate stimulated-emission-depletion microscopy of proteins and synchrotron X-ray fluorescence imaging of trace metals, both performed with 40 nm spatial resolution, on primary rat hippocampal neurons. We reveal the co-localization at the nanoscale of zinc and tubulin in dendrites with a molecular ratio of about one zinc atom per tubulin-αβ dimer. We observe the co-segregation of copper and F-actin within the nano-architecture of dendritic protrusions. In addition, zinc or copper chelation cause a decrease in the expression of cytoskeleton proteins in dendrites and spines. These results indicate new functions for zinc and copper in the modulation of the neuronal cytoskeleton morphology, a mechanism associated to structural plasticity.
Domart F., Cloetens P., Roudeau S., Carmona A., Verdier E., Choquet D., Ortega R. (2020)
Correlating STED and synchrotron XRF nano-imaging unveils cosegregation of metals and cytoskeleton proteins in dendrites.
eLife, 9:e62334. doi: 10.7554/eLife.62334
Perrin L., Roudeau S., Carmona A., Domart F., Petersen J.D., Bohic S., Yang Y., Cloetens P., Ortega R. (2017)
Zinc and copper effects on stability of tubulin and actin networks in dendrites and spines of hippocampal neurons.
ACS Chemical Neuroscience, 8, 1490-1499. doi: 10.1021/acschemneuro.6b00452