title: The neuronal K-Cl cotransporter KCC2 influences postsynaptic AMPA receptor content and lateral diffusion in dendritic spines.
abstract: 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.
authors: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche-S 839, F75005 Paris, France.
authors: Grégory
authors: G
authors: Gauvain
authors: Ingrid
authors: I
authors: Chamma
authors: Quentin
authors: Q
authors: Chevy
authors: Carolina
authors: C
authors: Cabezas
authors: Theano
authors: T
authors: Irinopoulou
authors: Natalia
authors: N
authors: Bodrug
authors: Michèle
authors: M
authors: Carnaud
authors: Sabine
authors: S
authors: Lévi
authors: Jean Christophe
authors: JC
authors: Poncer
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D049229:Dendritic Spines / Q000378:metabolism*; D004058:Diffusion; D006624:Hippocampus / Q000166:cytology; D042541:Intracellular Space / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism*; D027981:Symporters / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D000096922:K Cl- Cotransporters
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D018091:Receptors, AMPA; D027981:Symporters; D000096922:K Cl- Cotransporters