In:
Journal of Cell Biology, Rockefeller University Press, Vol. 219, No. 7 ( 2020-07-06)
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0021-9525
,
1540-8140
DOI:
10.1083/jcb.201909022
Sprache:
Englisch
Verlag:
Rockefeller University Press
Publikationsdatum:
2020
ZDB Id:
1421310-2
SSG:
12