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

• Published in: Neuron (Cambridge, Mass.) Vol. 86; no. 2; pp. 457 - 474
• Main Authors: Hoerndli, Frédéric J., Wang, Rui, Mellem, Jerry E., Kallarackal, Angy, Brockie, Penelope J., Thacker, Colin, Madsen, David M., Maricq, Andres V.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 22.04.2015; Elsevier Limited
• Subjects: Animals; Animals, Genetically Modified; Behavior; 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; Kinases; Kinesin - metabolism; Long-Term Potentiation - physiology; Mice; Mutation; Nervous system; Neuronal Plasticity - genetics; Neurons; Neurons - metabolism; Patch-Clamp Techniques; Potassium Channels, Voltage-Gated - physiology; Proteins; Receptors, Glutamate - metabolism; Regression analysis; Synapses - physiology
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2015.03.011

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.