Data from: HDAC1/2-dependent P0 expression maintains paranodal and nodal integrity independently of myelin stability through interactions with neurofascins

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.