10.5061/DRYAD.8F1BT
Brügger, Valérie
University of Fribourg
Engler, Stefanie
University of Fribourg
Pereira, Jorge A.
Ruff, Sophie
University of Fribourg
Horn, Michael
Welzl, Hans
University of Zurich
Münger, Emmanuelle
University of Fribourg
Vaquié, Adrien
University of Fribourg
Sidiropoulos, Páris N. M.
Egger, Boris
University of Fribourg
Yotovski, Peter
University of Fribourg
Filgueira, Luis
University of Fribourg
Somandin, Christian
Lühmann, Tessa C.
D’Antonio, Maurizio
Yamaguchi, Teppei
Matthias, Patrick
Suter, Ueli
Jacob, Claire
University of Fribourg
Data from: HDAC1/2-dependent P0 expression maintains paranodal and nodal
integrity independently of myelin stability through interactions with
neurofascins
Dryad
dataset
2016
Myelin protein zero
Paranodes
Mus musculus
Neurofascins
Schwann cells
Node of Ranvier
Homo Sapiens
Maintenance
Histone deacetylases
2016-08-24T00:00:00Z
2016-08-24T00:00:00Z
en
https://doi.org/10.1371/journal.pbio.1002258
74122034 bytes
1
CC0 1.0 Universal (CC0 1.0) Public Domain Dedication
The pathogenesis of peripheral neuropathies in adults is linked to
maintenance mechanisms that are not well understood. Here, we elucidate a
novel critical maintenance mechanism for Schwann cell (SC)–axon
interaction. Using mouse genetics, ablation of the transcriptional
regulators histone deacetylases 1 and 2 (HDAC1/2) in adult SCs severely
affected paranodal and nodal integrity and led to
demyelination/remyelination. Expression levels of the HDAC1/2 target gene
myelin protein zero (P0) were reduced by half, accompanied by altered
localization and stability of neurofascin (NFasc)155, NFasc186, and loss
of Caspr and septate-like junctions. We identify P0 as a novel binding
partner of NFasc155 and NFasc186, both in vivo and by in vitro adhesion
assay. Furthermore, we demonstrate that HDAC1/2-dependent P0 expression is
crucial for the maintenance of paranodal/nodal integrity and axonal
function through interaction of P0 with neurofascins. In addition, we show
that the latter mechanism is impaired by some P0 mutations that lead to
late onset Charcot-Marie-Tooth disease.
Underlying data main and supplementary figures2 Excel files with
underlying data of Figs. 1CEFGH, 2AD, 3AGH, 4AB, 5BEGI, 6F, 7F, 9BE,
S1ABC, S2BCD, S3ABCDE, S5, S6A, S7BC, S17BE, S18, and 2 video for Fig
1DDryad.zip