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 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.
Li
Hong
H
Institute of Biotechnology, University of Helsinki, Viikinkaari 4, FIN-00014, Helsinki, Finland.
Khirug
Stanislav
S
Cai
Chunlin
C
Ludwig
Anastasia
A
Blaesse
Peter
P
Kolikova
Julia
J
Afzalov
Ramil
R
Coleman
Sarah K
SK
Lauri
Sari
S
Airaksinen
Matti S
MS
Keinänen
Kari
K
Khiroug
Leonard
L
Saarma
Mart
M
Kaila
Kai
K
Rivera
Claudio
C
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology / Q000254:growth & development; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000502:physiology*; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure*; D049229:Dendritic Spines / Q000502:physiology*; D004622:Embryo, Mammalian; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008239:Lysine / Q000031:analogs & derivatives / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000502:physiology; D009419:Nerve Tissue Proteins; D009474:Neurons / Q000166:cytology*; D009479:Neuropeptides; D018408:Patch-Clamp Techniques / Q000379:methods; D027981:Symporters / Q000172:deficiency / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D014162:Transfection / Q000379:methods; D000096922:K Cl- Cotransporters
D003598:Cytoskeletal Proteins; D049452:Green Fluorescent Proteins; D008239:Lysine; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D027981:Symporters; D000096922:K Cl- Cotransporters; C120557:erythrocyte membrane protein band 4.1-like 1; C013411:biocytin