A Novel View on the Role of Intracellular Tails in Surface Delivery of the Potassium-Chloride Cotransporter KCC2

Perrine Friedel, Anastasia Ludwig, Christophe Pellegrino, Morgane Agez, Anass Jawhari, Juan Claudio Rivera Baeza, Igor Medina

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

Sammanfattning

A plethora of neurological disorders are associated with alterations in the expression and localization of potassium-chloride cotransporter type 2 (KCC2), making KCC2 a critical player in neuronal function and an attractive target for therapeutic treatment. The activity of KCC2 is determined primarily by the rates of its surface insertion and internalization. Currently the domains of KCC2 dictating its trafficking and endocytosis are unknown. Here, using live-cell immunolabeling and biotinylation of KCC2 proteins expressed in murine neuroblastoma N2a cells, human embryonic kidney 293 cells, or primary cultures of rat hippocampal neurons, we identified a novel role for the intracellular N and C termini in differentially regulating KCC2 surface expression. We report that the N terminus is required for KCC2 insertion into the plasma membrane, whereas the C terminus is critical for the membrane stability of KCC2. Our results provide novel insights into the structure–function role of specific KCC2 domains and open perspectives in exploring structural organization of this protein.
Originalspråkengelska
ArtikelnummerUNSP e0055
TidskrifteNeuro
Volym4
Utgåva4
Antal sidor19
ISSN2373-2822
DOI
StatusPublicerad - jul 2017
MoE-publikationstypA1 Tidskriftsartikel-refererad

Vetenskapsgrenar

  • 3112 Neurovetenskaper

Citera det här

Friedel, Perrine ; Ludwig, Anastasia ; Pellegrino, Christophe ; Agez, Morgane ; Jawhari, Anass ; Rivera Baeza, Juan Claudio ; Medina, Igor. / A Novel View on the Role of Intracellular Tails in Surface Delivery of the Potassium-Chloride Cotransporter KCC2. I: eNeuro. 2017 ; Vol. 4, Nr. 4.
@article{bf98571087e84b81a791d7a374323b45,
title = "A Novel View on the Role of Intracellular Tails in Surface Delivery of the Potassium-Chloride Cotransporter KCC2",
abstract = "A plethora of neurological disorders are associated with alterations in the expression and localization of potassium-chloride cotransporter type 2 (KCC2), making KCC2 a critical player in neuronal function and an attractive target for therapeutic treatment. The activity of KCC2 is determined primarily by the rates of its surface insertion and internalization. Currently the domains of KCC2 dictating its trafficking and endocytosis are unknown. Here, using live-cell immunolabeling and biotinylation of KCC2 proteins expressed in murine neuroblastoma N2a cells, human embryonic kidney 293 cells, or primary cultures of rat hippocampal neurons, we identified a novel role for the intracellular N and C termini in differentially regulating KCC2 surface expression. We report that the N terminus is required for KCC2 insertion into the plasma membrane, whereas the C terminus is critical for the membrane stability of KCC2. Our results provide novel insights into the structure–function role of specific KCC2 domains and open perspectives in exploring structural organization of this protein.",
keywords = "3112 Neurosciences",
author = "Perrine Friedel and Anastasia Ludwig and Christophe Pellegrino and Morgane Agez and Anass Jawhari and {Rivera Baeza}, {Juan Claudio} and Igor Medina",
year = "2017",
month = "7",
doi = "10.1523/ENEURO.0055-17.2017",
language = "English",
volume = "4",
journal = "eNeuro",
issn = "2373-2822",
publisher = "Society of Neuroscience",
number = "4",

}

A Novel View on the Role of Intracellular Tails in Surface Delivery of the Potassium-Chloride Cotransporter KCC2. / Friedel, Perrine; Ludwig, Anastasia; Pellegrino, Christophe; Agez, Morgane; Jawhari, Anass; Rivera Baeza, Juan Claudio; Medina, Igor.

I: eNeuro, Vol. 4, Nr. 4, UNSP e0055, 07.2017.

Forskningsoutput: TidskriftsbidragArtikelVetenskapligPeer review

TY - JOUR

T1 - A Novel View on the Role of Intracellular Tails in Surface Delivery of the Potassium-Chloride Cotransporter KCC2

AU - Friedel, Perrine

AU - Ludwig, Anastasia

AU - Pellegrino, Christophe

AU - Agez, Morgane

AU - Jawhari, Anass

AU - Rivera Baeza, Juan Claudio

AU - Medina, Igor

PY - 2017/7

Y1 - 2017/7

N2 - A plethora of neurological disorders are associated with alterations in the expression and localization of potassium-chloride cotransporter type 2 (KCC2), making KCC2 a critical player in neuronal function and an attractive target for therapeutic treatment. The activity of KCC2 is determined primarily by the rates of its surface insertion and internalization. Currently the domains of KCC2 dictating its trafficking and endocytosis are unknown. Here, using live-cell immunolabeling and biotinylation of KCC2 proteins expressed in murine neuroblastoma N2a cells, human embryonic kidney 293 cells, or primary cultures of rat hippocampal neurons, we identified a novel role for the intracellular N and C termini in differentially regulating KCC2 surface expression. We report that the N terminus is required for KCC2 insertion into the plasma membrane, whereas the C terminus is critical for the membrane stability of KCC2. Our results provide novel insights into the structure–function role of specific KCC2 domains and open perspectives in exploring structural organization of this protein.

AB - A plethora of neurological disorders are associated with alterations in the expression and localization of potassium-chloride cotransporter type 2 (KCC2), making KCC2 a critical player in neuronal function and an attractive target for therapeutic treatment. The activity of KCC2 is determined primarily by the rates of its surface insertion and internalization. Currently the domains of KCC2 dictating its trafficking and endocytosis are unknown. Here, using live-cell immunolabeling and biotinylation of KCC2 proteins expressed in murine neuroblastoma N2a cells, human embryonic kidney 293 cells, or primary cultures of rat hippocampal neurons, we identified a novel role for the intracellular N and C termini in differentially regulating KCC2 surface expression. We report that the N terminus is required for KCC2 insertion into the plasma membrane, whereas the C terminus is critical for the membrane stability of KCC2. Our results provide novel insights into the structure–function role of specific KCC2 domains and open perspectives in exploring structural organization of this protein.

KW - 3112 Neurosciences

U2 - 10.1523/ENEURO.0055-17.2017

DO - 10.1523/ENEURO.0055-17.2017

M3 - Article

VL - 4

JO - eNeuro

JF - eNeuro

SN - 2373-2822

IS - 4

M1 - UNSP e0055

ER -