Loss of non-canonical KCC2 functions promotes developmental apoptosis of cortical projection neurons

Show full item record



Permalink

http://hdl.handle.net/10138/318336

Citation

Mavrovic , M , Uvarov , P , Delpire , E , Vutskits , L , Kaila , K & Puskarjov , M 2020 , ' Loss of non-canonical KCC2 functions promotes developmental apoptosis of cortical projection neurons ' , EMBO Reports , vol. 21 , no. 4 , 48880 . https://doi.org/10.15252/embr.201948880

Title: Loss of non-canonical KCC2 functions promotes developmental apoptosis of cortical projection neurons
Author: Mavrovic, Martina; Uvarov, Pavel; Delpire, Eric; Vutskits, Laszlo; Kaila, Kai; Puskarjov, Martin
Contributor organization: Molecular and Integrative Biosciences Research Programme
Neuroscience Center
Laboratory of Neurobiology
Date: 2020-04-03
Language: eng
Number of pages: 13
Belongs to series: EMBO Reports
ISSN: 1469-221X
DOI: https://doi.org/10.15252/embr.201948880
URI: http://hdl.handle.net/10138/318336
Abstract: KCC2, encoded in humans by the SLC12A5 gene, is a multifunctional neuron-specific protein initially identified as the chloride (Cl-) extruder critical for hyperpolarizing GABA(A) receptor currents. Independently of its canonical function as a K-Cl cotransporter, KCC2 regulates the actin cytoskeleton via molecular interactions mediated through its large intracellular C-terminal domain (CTD). Contrary to the common assumption that embryonic neocortical projection neurons express KCC2 at non-significant levels, here we show that loss of KCC2 enhances apoptosis of late-born upper-layer cortical projection neurons in the embryonic brain. In utero electroporation of plasmids encoding truncated, transport-dead KCC2 constructs retaining the CTD was as efficient as of that encoding full-length KCC2 in preventing elimination of migrating projection neurons upon conditional deletion of KCC2. This was in contrast to the effect of a full-length KCC2 construct bearing a CTD missense mutation (KCC2(R952H)), which disrupts cytoskeletal interactions and has been found in patients with neurological and psychiatric disorders, notably seizures and epilepsy. Together, our findings indicate ion transport-independent, CTD-mediated regulation of developmental apoptosis by KCC2 in migrating cortical projection neurons.
Subject: CL-COTRANSPORTER KCC2
EXPRESSION
EXTRUSION
GABA
HIPPOCAMPAL-NEURONS
IN-VIVO
KCC2
MATURATION
NEURAL DEVELOPMENT
OHTAHARA SYNDROME
PROGRAMMED CELL-DEATH
cell death
chloride
cofilin
1182 Biochemistry, cell and molecular biology
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: acceptedVersion


Files in this item

Total number of downloads: Loading...

Files Size Format View
Mavrovic_et_al._EMBOr_accepted_manuscript.pdf 22.74Mb PDF View/Open

This item appears in the following Collection(s)

Show full item record