%T Neuronal activity disrupts myelinated axon integrity in the absence of NKCC1b
%V 219
%A KLH Marshall-Phelps
%A L Kegel
%A M Baraban
%A T Ruhwedel
%A RG Almeida
%A M Rubio-Brotons
%A A Klingseisen
%A SK Benito-Kwiecinski
%A JJ Early
%A JM Bin
%A D Suminaite
%A MR Livesey
%A W Möbius
%A RJ Poole
%A DA Lyons
%N 7
%D 2020
%K Cell signaling
%J Journal of Cell Biology
%L discovery10098423
%C United States
%X Through a genetic screen in zebrafish, we identified a mutant with disruption to myelin in both the CNS and PNS caused by a mutation in a previously uncharacterized gene, slc12a2b, predicted to encode a Na+, K+, and Cl− (NKCC) cotransporter, NKCC1b. slc12a2b/NKCC1b mutants exhibited a severe and progressive pathology in the PNS, characterized by dysmyelination and swelling of the periaxonal space at the axon–myelin interface. Cell-type–specific loss of slc12a2b/NKCC1b in either neurons or myelinating Schwann cells recapitulated these pathologies. Given that NKCC1 is critical for ion homeostasis, we asked whether the disruption to myelinated axons in slc12a2b/NKCC1b mutants is affected by neuronal activity. Strikingly, we found that blocking neuronal activity completely prevented and could even rescue the pathology in slc12a2b/NKCC1b mutants. Together, our data indicate that NKCC1b is required to maintain neuronal activity–related solute homeostasis at the axon–myelin interface, and the integrity of myelinated axons.
%O This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).