KCC2 regulates actin dynamics in dendritic spines via interaction with β-PIX

Olaya Llano Sanchez, Sergey Smirnov, Shetal Soni, Andrey Golubtsov, Isabelle Guillemin, Pirta Elina Hotulainen, Igor Medina, Hans Gerd Nothwang, Juan Claudio Rivera Baeza, Anastasia Ludwig

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Chloride extrusion in mature neurons is largely mediated by the neuron-specific potassium-chloride cotransporter KCC2. In addition, independently of its chloride transport function, KCC2 regulates the development and morphology of dendritic spines through structural interactions with the actin cytoskeleton. The mechanism of this effect remains largely unknown. In this paper, we show a novel pathway for KCC2-mediated regulation of the actin cytoskeleton in neurons. We found that KCC2, through interaction with the b isoform of Rac/Cdc42 guanine nucleotide exchange factor β-PIX, regulates the activity of Rac1 GTPase and the phosphorylation of one of the major actin-regulating proteins, cofilin-1. KCC2-deficient neurons had abnormally high levels of phosphorylated cofilin-1. Consistently, dendritic spines of these neurons exhibited a large pool of stable actin, resulting in reduced spine motility and diminished density of functional synapses. In conclusion, we describe a novel signaling pathway that couples KCC2 to the cytoskeleton and regulates the formation of glutamatergic synapses.
Original languageEnglish
JournalJournal of Cell Biology
Volume209
Issue number5
Pages (from-to)671-686
Number of pages16
ISSN0021-9525
DOIs
Publication statusPublished - 8 Jun 2015
MoE publication typeA1 Journal article-refereed

Fields of Science

  • 1182 Biochemistry, cell and molecular biology

Cite this

Llano Sanchez, Olaya ; Smirnov, Sergey ; Soni, Shetal ; Golubtsov, Andrey ; Guillemin, Isabelle ; Hotulainen, Pirta Elina ; Medina, Igor ; Nothwang, Hans Gerd ; Rivera Baeza, Juan Claudio ; Ludwig, Anastasia. / KCC2 regulates actin dynamics in dendritic spines via interaction with β-PIX. In: Journal of Cell Biology. 2015 ; Vol. 209, No. 5. pp. 671-686.
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title = "KCC2 regulates actin dynamics in dendritic spines via interaction with β-PIX",
abstract = "Chloride extrusion in mature neurons is largely mediated by the neuron-specific potassium-chloride cotransporter KCC2. In addition, independently of its chloride transport function, KCC2 regulates the development and morphology of dendritic spines through structural interactions with the actin cytoskeleton. The mechanism of this effect remains largely unknown. In this paper, we show a novel pathway for KCC2-mediated regulation of the actin cytoskeleton in neurons. We found that KCC2, through interaction with the b isoform of Rac/Cdc42 guanine nucleotide exchange factor β-PIX, regulates the activity of Rac1 GTPase and the phosphorylation of one of the major actin-regulating proteins, cofilin-1. KCC2-deficient neurons had abnormally high levels of phosphorylated cofilin-1. Consistently, dendritic spines of these neurons exhibited a large pool of stable actin, resulting in reduced spine motility and diminished density of functional synapses. In conclusion, we describe a novel signaling pathway that couples KCC2 to the cytoskeleton and regulates the formation of glutamatergic synapses.",
keywords = "1182 Biochemistry, cell and molecular biology",
author = "{Llano Sanchez}, Olaya and Sergey Smirnov and Shetal Soni and Andrey Golubtsov and Isabelle Guillemin and Hotulainen, {Pirta Elina} and Igor Medina and Nothwang, {Hans Gerd} and {Rivera Baeza}, {Juan Claudio} and Anastasia Ludwig",
year = "2015",
month = "6",
day = "8",
doi = "10.1083/jcb.201411008",
language = "English",
volume = "209",
pages = "671--686",
journal = "Journal of Cell Biology",
issn = "0021-9525",
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Llano Sanchez, O, Smirnov, S, Soni, S, Golubtsov, A, Guillemin, I, Hotulainen, PE, Medina, I, Nothwang, HG, Rivera Baeza, JC & Ludwig, A 2015, 'KCC2 regulates actin dynamics in dendritic spines via interaction with β-PIX', Journal of Cell Biology, vol. 209, no. 5, pp. 671-686. https://doi.org/10.1083/jcb.201411008

KCC2 regulates actin dynamics in dendritic spines via interaction with β-PIX. / Llano Sanchez, Olaya; Smirnov, Sergey; Soni, Shetal; Golubtsov, Andrey; Guillemin, Isabelle; Hotulainen, Pirta Elina; Medina, Igor; Nothwang, Hans Gerd; Rivera Baeza, Juan Claudio; Ludwig, Anastasia.

In: Journal of Cell Biology, Vol. 209, No. 5, 08.06.2015, p. 671-686.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - KCC2 regulates actin dynamics in dendritic spines via interaction with β-PIX

AU - Llano Sanchez, Olaya

AU - Smirnov, Sergey

AU - Soni, Shetal

AU - Golubtsov, Andrey

AU - Guillemin, Isabelle

AU - Hotulainen, Pirta Elina

AU - Medina, Igor

AU - Nothwang, Hans Gerd

AU - Rivera Baeza, Juan Claudio

AU - Ludwig, Anastasia

PY - 2015/6/8

Y1 - 2015/6/8

N2 - Chloride extrusion in mature neurons is largely mediated by the neuron-specific potassium-chloride cotransporter KCC2. In addition, independently of its chloride transport function, KCC2 regulates the development and morphology of dendritic spines through structural interactions with the actin cytoskeleton. The mechanism of this effect remains largely unknown. In this paper, we show a novel pathway for KCC2-mediated regulation of the actin cytoskeleton in neurons. We found that KCC2, through interaction with the b isoform of Rac/Cdc42 guanine nucleotide exchange factor β-PIX, regulates the activity of Rac1 GTPase and the phosphorylation of one of the major actin-regulating proteins, cofilin-1. KCC2-deficient neurons had abnormally high levels of phosphorylated cofilin-1. Consistently, dendritic spines of these neurons exhibited a large pool of stable actin, resulting in reduced spine motility and diminished density of functional synapses. In conclusion, we describe a novel signaling pathway that couples KCC2 to the cytoskeleton and regulates the formation of glutamatergic synapses.

AB - Chloride extrusion in mature neurons is largely mediated by the neuron-specific potassium-chloride cotransporter KCC2. In addition, independently of its chloride transport function, KCC2 regulates the development and morphology of dendritic spines through structural interactions with the actin cytoskeleton. The mechanism of this effect remains largely unknown. In this paper, we show a novel pathway for KCC2-mediated regulation of the actin cytoskeleton in neurons. We found that KCC2, through interaction with the b isoform of Rac/Cdc42 guanine nucleotide exchange factor β-PIX, regulates the activity of Rac1 GTPase and the phosphorylation of one of the major actin-regulating proteins, cofilin-1. KCC2-deficient neurons had abnormally high levels of phosphorylated cofilin-1. Consistently, dendritic spines of these neurons exhibited a large pool of stable actin, resulting in reduced spine motility and diminished density of functional synapses. In conclusion, we describe a novel signaling pathway that couples KCC2 to the cytoskeleton and regulates the formation of glutamatergic synapses.

KW - 1182 Biochemistry, cell and molecular biology

U2 - 10.1083/jcb.201411008

DO - 10.1083/jcb.201411008

M3 - Article

VL - 209

SP - 671

EP - 686

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 5

ER -