eprintid: 10098423
rev_number: 14
eprint_status: archive
userid: 608
dir: disk0/10/09/84/23
datestamp: 2020-05-27 11:32:46
lastmod: 2021-09-25 23:11:01
status_changed: 2020-05-27 11:32:46
type: article
metadata_visibility: show
creators_name: Marshall-Phelps, KLH
creators_name: Kegel, L
creators_name: Baraban, M
creators_name: Ruhwedel, T
creators_name: Almeida, RG
creators_name: Rubio-Brotons, M
creators_name: Klingseisen, A
creators_name: Benito-Kwiecinski, SK
creators_name: Early, JJ
creators_name: Bin, JM
creators_name: Suminaite, D
creators_name: Livesey, MR
creators_name: Möbius, W
creators_name: Poole, RJ
creators_name: Lyons, DA
title: Neuronal activity disrupts myelinated axon integrity in the absence of NKCC1b
ispublished: pub
divisions: UCL
divisions: B02
divisions: C08
divisions: D09
divisions: F96
keywords: Cell signaling
note: This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
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.
date: 2020-07-06
date_type: published
official_url: https://doi.org/10.1083/jcb.201909022
oa_status: green
full_text_type: pub
language: eng
primo: open
primo_central: open_green
verified: verified_manual
elements_id: 1783207
doi: 10.1083/jcb.201909022
pii: 151733
lyricists_name: Poole, Richard
lyricists_id: RPOOL83
actors_name: Flynn, Bernadette
actors_id: BFFLY94
actors_role: owner
full_text_status: public
publication: Journal of Cell Biology
volume: 219
number: 7
article_number: e201909022
event_location: United States
citation:        Marshall-Phelps, KLH;    Kegel, L;    Baraban, M;    Ruhwedel, T;    Almeida, RG;    Rubio-Brotons, M;    Klingseisen, A;                                 ... Lyons, DA; + view all <#>        Marshall-Phelps, KLH;  Kegel, L;  Baraban, M;  Ruhwedel, T;  Almeida, RG;  Rubio-Brotons, M;  Klingseisen, A;  Benito-Kwiecinski, SK;  Early, JJ;  Bin, JM;  Suminaite, D;  Livesey, MR;  Möbius, W;  Poole, RJ;  Lyons, DA;   - view fewer <#>    (2020)    Neuronal activity disrupts myelinated axon integrity in the absence of NKCC1b.                   Journal of Cell Biology , 219  (7)    , Article e201909022.  10.1083/jcb.201909022 <https://doi.org/10.1083/jcb.201909022>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/10098423/1/jcb_201909022.pdf