The neuronal K-Cl cotransporter KCC2 influences postsynaptic AMPA receptor content and lateral diffusion in dendritic spines
Proceedings of the National Academy of Sciences. 2011-08-30; 108(37): 15474-15479
DOI: 10.1073/pnas.1107893108
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1. Proc Natl Acad Sci U S A. 2011 Sep 13;108(37):15474-9. doi:
10.1073/pnas.1107893108. Epub 2011 Aug 30.
The neuronal K-Cl cotransporter KCC2 influences postsynaptic AMPA receptor
content and lateral diffusion in dendritic spines.
Gauvain G(1), Chamma I, Chevy Q, Cabezas C, Irinopoulou T, Bodrug N, Carnaud M,
Lévi S, Poncer JC.
Author information:
(1)Institut National de la Santé et de la Recherche Médicale, Unité Mixte de
Recherche-S 839, F75005 Paris, France.
Erratum in
Proc Natl Acad Sci U S A. 2015 Oct 6;112(40):E5554.
The K-Cl cotransporter KCC2 plays an essential role in neuronal chloride
homeostasis, and thereby influences the efficacy and polarity of GABA signaling.
Although KCC2 is expressed throughout the somatodendritic membrane, it is
remarkably enriched in dendritic spines, which host most glutamatergic synapses
in cortical neurons. KCC2 has been shown to influence spine morphogenesis and
functional maturation in developing neurons, but its function in mature dendritic
spines remains unknown. Here, we report that suppressing KCC2 expression
decreases the efficacy of excitatory synapses in mature hippocampal neurons. This
effect correlates with a reduced postsynaptic aggregation of GluR1-containing
AMPA receptors and is mimicked by a dominant negative mutant of KCC2 interaction
with cytoskeleton but not by pharmacological suppression of KCC2 function.
Single-particle tracking experiments reveal that suppressing KCC2 increases
lateral diffusion of the mobile fraction of AMPA receptor subunit GluR1 in spines
but not in adjacent dendritic shafts. Increased diffusion was also observed for
transmembrane but not membrane-anchored recombinant neuronal cell adhesion
molecules. We suggest that KCC2, likely through interactions with the actin
cytoskeleton, hinders transmembrane protein diffusion, and thereby contributes to
their confinement within dendritic spines.
DOI: 10.1073/pnas.1107893108
PMCID: PMC3174661
PMID: 21878564 [Indexed for MEDLINE]