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Journal Article

Neuronal activity disrupts myelinated axon integrity in the absence of NKCC1b

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Ruhwedel,  T.
Electron microscopy, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

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Möbius,  W.
Electron microscopy, Neurogenetics, Max Planck Institute of Experimental Medicine, Max Planck Society;

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Citation

Marshall-Phelps, K. L. H., Kegel, L., Baraban, M., Ruhwedel, T., Almeida, R. G., Rubio-Brotons, M., et al. (2020). Neuronal activity disrupts myelinated axon integrity in the absence of NKCC1b. Journal of Cell Biology, 219(7): e201909022. doi:10.1083/jcb.201909022.


Cite as: https://hdl.handle.net/21.11116/0000-000A-CCDD-8
Abstract
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.