KCC2 Interacts with the Dendritic Cytoskeleton to Promote Spine Development

The neuron-specific K-Cl cotransporter, KCC2, induces a developmental shift to render GABAergic transmission from depolarizing to hyperpolarizing. Now we demonstrate that KCC2, independently of its Cl − transport function, is a key factor in the maturation of dendritic spines. This morphogenic role...

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Bibliographic Details
Published in:Neuron (Cambridge, Mass.) Mass.), 2007-12, Vol.56 (6), p.1019-1033
Main Authors: Li, Hong, Khirug, Stanislav, Cai, Chunlin, Ludwig, Anastasia, Blaesse, Peter, Kolikova, Julia, Afzalov, Ramil, Coleman, Sarah K., Lauri, Sari, Airaksinen, Matti S., Keinänen, Kari, Khiroug, Leonard, Saarma, Mart, Kaila, Kai, Rivera, Claudio
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
CELLBIO
Cells, Cultured
Cerebral Cortex - cytology
Cerebral Cortex - embryology
Cerebral Cortex - growth & development
Cytoskeletal Proteins
Cytoskeleton
Cytoskeleton - physiology
Dendrites - metabolism
Dendrites - ultrastructure
Dendritic Spines - physiology
Embryo, Mammalian
Excitatory Postsynaptic Potentials - drug effects
Excitatory Postsynaptic Potentials - physiology
Excitatory Postsynaptic Potentials - radiation effects
Green Fluorescent Proteins - metabolism
Humans
Immunization
In Vitro Techniques
K Cl- Cotransporters
Lysine - analogs & derivatives
Lysine - metabolism
Membrane Proteins
Mice
Mice, Knockout
Microscopy
Mutation - physiology
Nerve Tissue Proteins
Neurons
Neurons - cytology
Neuropeptides
Patch-Clamp Techniques - methods
Proteins
Symporters - deficiency
Symporters - physiology
Synaptic Transmission - physiology
SYSBIO
SYSNEURO
Transfection - methods
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Summary:The neuron-specific K-Cl cotransporter, KCC2, induces a developmental shift to render GABAergic transmission from depolarizing to hyperpolarizing. Now we demonstrate that KCC2, independently of its Cl − transport function, is a key factor in the maturation of dendritic spines. This morphogenic role of KCC2 in the development of excitatory synapses is mediated by structural interactions between KCC2 and the spine cytoskeleton. Here, the binding of KCC2 C-terminal domain to the cytoskeleton-associated protein 4.1N may play an important role. A more general conclusion based on our data is that KCC2 acts as a synchronizing factor in the functional development of glutamatergic and GABAergic synapses in cortical neurons and networks.
ISSN:0896-6273
1097-4199
DOI:10.1016/j.neuron.2007.10.039