TY  - JOUR
VL  - 219
N1  - This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
JF  - Journal of Cell Biology
A1  - Marshall-Phelps, KLH
A1  - Kegel, L
A1  - Baraban, M
A1  - Ruhwedel, T
A1  - Almeida, RG
A1  - Rubio-Brotons, M
A1  - Klingseisen, A
A1  - Benito-Kwiecinski, SK
A1  - Early, JJ
A1  - Bin, JM
A1  - Suminaite, D
A1  - Livesey, MR
A1  - Möbius, W
A1  - Poole, RJ
A1  - Lyons, DA
KW  - Cell signaling
Y1  - 2020/07/06/
TI  - Neuronal activity disrupts myelinated axon integrity in the absence of NKCC1b
AV  - public
N2  - 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.
IS  - 7
UR  - https://doi.org/10.1083/jcb.201909022
ID  - discovery10098423
ER  -