KCC2 interacts with the dendritic cytoskeleton to promote spine development

Neuron. 2007 Dec 20;56(6):1019-33. doi: 10.1016/j.neuron.2007.10.039.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cells, Cultured
  • Cerebral Cortex / cytology
  • Cerebral Cortex / embryology
  • Cerebral Cortex / growth & development
  • Cytoskeletal Proteins
  • 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
  • In Vitro Techniques
  • Lysine / analogs & derivatives
  • Lysine / metabolism
  • Membrane Proteins
  • Mice
  • Mice, Knockout
  • Mutation / physiology
  • Nerve Tissue Proteins
  • Neurons / cytology*
  • Neuropeptides
  • Patch-Clamp Techniques / methods
  • Symporters / deficiency
  • Symporters / physiology*
  • Synaptic Transmission / physiology
  • Transfection / methods

Substances

  • Cytoskeletal Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Neuropeptides
  • Symporters
  • erythrocyte membrane protein band 4.1-like 1
  • potassium-chloride symporters
  • Green Fluorescent Proteins
  • biocytin
  • Lysine