PUBLICATION
Neuronal activity disrupts myelinated axon integrity in the absence of NKCC1b
- Authors
- Marshall-Phelps, K.L.H., Kegel, L., Baraban, M., Ruhwedel, T., Almeida, R.G., Rubio-Brotons, M., Klingseisen, A., Benito-Kwiecinski, S.K., Early, J.J., Bin, J.M., Suminaite, D., Livesey, M.R., Möbius, W., Poole, R.J., Lyons, D.A.
- ID
- ZDB-PUB-200505-3
- Date
- 2020
- Source
- The Journal of cell biology 219(7): (Journal)
- Registered Authors
- Almeida, Rafael, Kegel, Linde, Lyons, David A., Poole, Richard
- Keywords
- none
- MeSH Terms
-
- Action Potentials
- Amino Acid Sequence
- Animals
- Animals, Genetically Modified
- Axons/drug effects
- Axons/metabolism*
- Axons/ultrastructure
- Central Nervous System/drug effects
- Central Nervous System/metabolism
- Central Nervous System/pathology
- Embryo, Nonmammalian
- Gene Expression Regulation, Developmental
- Humans
- Mutation
- Myelin Sheath/drug effects
- Myelin Sheath/metabolism*
- Myelin Sheath/ultrastructure
- Neurons/drug effects
- Neurons/metabolism*
- Neurons/ultrastructure
- Peripheral Nervous System/drug effects
- Peripheral Nervous System/metabolism
- Peripheral Nervous System/pathology
- Schwann Cells/drug effects
- Schwann Cells/metabolism*
- Schwann Cells/ultrastructure
- Sequence Alignment
- Sequence Homology, Amino Acid
- Signal Transduction
- Sodium Channel Blockers/toxicity
- Solute Carrier Family 12, Member 2/deficiency
- Solute Carrier Family 12, Member 2/genetics*
- Tetrodotoxin/toxicity
- Zebrafish
- Zebrafish Proteins/deficiency
- Zebrafish Proteins/genetics*
- PubMed
- 32364583 Full text @ J. Cell Biol.
Citation
Marshall-Phelps, K.L.H., Kegel, L., Baraban, M., Ruhwedel, T., Almeida, R.G., Rubio-Brotons, M., Klingseisen, A., Benito-Kwiecinski, S.K., Early, J.J., Bin, J.M., Suminaite, D., Livesey, M.R., Möbius, W., Poole, R.J., Lyons, D.A. (2020) Neuronal activity disrupts myelinated axon integrity in the absence of NKCC1b. The Journal of cell biology. 219(7).
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping