Research Article: Weak power frequency magnetic fields induce microtubule cytoskeleton reorganization depending on the epidermal growth factor receptor and the calcium related signaling

Date Published: October 12, 2018

Publisher: Public Library of Science

Author(s): Xia Wu, Juan Du, Weitao Song, Meiping Cao, Shude Chen, Ruohong Xia, Laszlo Buday.

http://doi.org/10.1371/journal.pone.0205569

Abstract

We have shown previously that a weak 50 Hz magnetic field (MF) invoked the actin-cytoskeleton, and provoked cell migration at the cell level, probably through activating the epidermal growth factor receptor (EGFR) related motility pathways. However, whether the MF also affects the microtubule (MT)-cytoskeleton is still unknown. In this article, we continuously investigate the effects of 0.4 mT, 50 Hz MF on the MT, and try to understand if the MT effects are also associated with the EGFR pathway as the actin-cytoskeleton effects were. Our results strongly suggest that the MF effects are similar to that of EGF stimulation on the MT cytoskeleton, showing that 1) the MF suppressed MT in multiple cell types including PC12 and FL; 2) the MF promoted the clustering of the EGFR at the protein and the cell levels, in a similar way of that EGF did but with higher sensitivity to PD153035 inhibition, and triggered EGFR phosphorylation on sites of Y1173 and S1046/1047; 3) these effects were strongly depending on the Ca2+ signaling through the L-type calcium channel (LTCC) phosphorylation and elevation of the intracellular Ca2+ level. Strong associations were observed between EGFR and the Ca2+ signaling to regulate the MF-induced-reorganization of the cytoskeleton network, via phosphorylating the signaling proteins in the two pathways, including a significant MT protein, tau. These results strongly suggest that the MF activates the overall cytoskeleton in the absence of EGF, through a mechanism related to both the EGFR and the LTCC/Ca2+ signaling pathways.

Partial Text

The cell motility depends on the transformation and reorganization of the cytoskeleton network, which mainly consists of actin filaments (F-actin), microtubules (MT), and intermediate filaments. In stationary state, cells usually have obvious thick stress fiber bundles across cell centers, polarized MT distributed from cell center to periphery, and focal adhesions (FA) scattered all over the cell; while in migrating cells, the cytoskeleton is reorganized with F-actin much thinner in cell centers while denser in lamellipodia, MT scarcely reaching cell periphery, and FA more in leading edge and less in rear direction [1, 2].

Taking together with our previous results [13], we showed that the MF, in a way similar to EGF but independent of the EGFR ligand, provoked both F-actin and MT cytoskeleton into a migrating/ready-to-migration state in epithelial and neuron cells. We report in this paper as the first-hand but primary evidence that the MF exposure induces the MT reorganization via activation of both the EGFR-PKC-MAPK/Erk and the Ca2+-CaMKII-MAPK/Erk pathways, and cross talks between them (Fig 9). Meanwhile, we have also shown that MF induces the formation and redistribution of focal adhesions, possibly through proteins paxillin and FAK, which are under the regulation of EGFR [62]. Relying on these EGFR and Ca2+ pathways and the crosstalk between them, the MF signal is transformed into biological signal and transmitted along the signal transduction cascades. In this manner, the effects of MF could be exaggerated and might finally exert influence to activate the overall F-actin- and MT-cytoskeleton, to trigger the growth of protrusional structures and focal adhesions, and to improve the cell migration in different cell lines.

 

Source:

http://doi.org/10.1371/journal.pone.0205569

 

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