Neuronal Activity and CaMKII Regulate Kinesin-Mediated Transport of Synaptic AMPARs

Neuron. 2015 Apr 22;86(2):457-74. doi: 10.1016/j.neuron.2015.03.011. Epub 2015 Apr 2.

Abstract

Excitatory glutamatergic synaptic transmission is critically dependent on maintaining an optimal number of postsynaptic AMPA receptors (AMPARs) at each synapse of a given neuron. Here, we show that presynaptic activity, postsynaptic potential, voltage-gated calcium channels (VGCCs) and UNC-43, the C. elegans homolog of CaMKII, control synaptic strength by regulating motor-driven AMPAR transport. Genetic mutations in unc-43, or spatially and temporally restricted inactivation of UNC-43/CaMKII, revealed its essential roles in the transport of AMPARs from the cell body and in the insertion and removal of synaptic AMPARs. We found that an essential target of UNC-43/CaMKII is kinesin light chain and that mouse CaMKII rescued unc-43 mutants, suggesting conservation of function. Transient expression of UNC-43/CaMKII in adults rescued the transport defects, while optogenetic stimulation of select synapses revealed CaMKII's role in activity-dependent plasticity. Our results demonstrate unanticipated, fundamentally important roles for UNC-43/CaMKII in the regulation of synaptic strength.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Biological Transport / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / genetics*
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
  • Kinesin / metabolism*
  • Long-Term Potentiation / physiology
  • Mice
  • Mutation
  • Neuronal Plasticity / genetics
  • Neurons / metabolism*
  • Patch-Clamp Techniques
  • Potassium Channels, Voltage-Gated / physiology*
  • Receptors, Glutamate / metabolism*
  • Synapses / physiology

Substances

  • Caenorhabditis elegans Proteins
  • Potassium Channels, Voltage-Gated
  • Receptors, Glutamate
  • Calcium-Calmodulin-Dependent Protein Kinase Type 2
  • unc-43 protein, C elegans
  • Kinesin