Unknown

Dataset Information

0

Neuronal activity disrupts myelinated axon integrity in the absence of NKCC1b.


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.

SUBMITTER: Marshall-Phelps KLH 

PROVIDER: S-EPMC7337504 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications


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 myelin  ...[more]

Similar Datasets

| S-EPMC5661983 | biostudies-literature
| S-EPMC5289982 | biostudies-literature
| S-EPMC3464962 | biostudies-literature
| S-EPMC1166590 | biostudies-literature
| S-EPMC5612983 | biostudies-literature
| S-EPMC4414883 | biostudies-literature
| S-EPMC3197268 | biostudies-literature
| S-EPMC3839048 | biostudies-literature
| S-EPMC10774424 | biostudies-literature
| S-EPMC5778130 | biostudies-literature