title: Neuronal Activity and CaMKII Regulate Kinesin-Mediated Transport of Synaptic AMPARs.
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.
authors.affiliation: Department of Biology and Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112-0840, USA.
authors.forename: Frédéric J
authors.initials: FJ
authors.lastname: Hoerndli
authors.affiliation: Department of Biology and Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112-0840, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Biology and Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112-0840, USA.
authors.forename: Jerry E
authors.initials: JE
authors.lastname: Mellem
authors.affiliation: Department of Biology and Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112-0840, USA.
authors.forename: Angy
authors.initials: A
authors.lastname: Kallarackal
authors.affiliation: Department of Biology and Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112-0840, USA.
authors.forename: Penelope J
authors.initials: PJ
authors.lastname: Brockie
authors.affiliation: Department of Biology and Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112-0840, USA.
authors.forename: Colin
authors.initials: C
authors.lastname: Thacker
authors.affiliation: Department of Biology and Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112-0840, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Madsen
authors.affiliation: Department of Biology and Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112-0840, USA. Electronic address: maricq@biology.utah.edu.
authors.forename: Andres V
authors.initials: AV
authors.lastname: Maricq
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001692:Biological Transport / Q000235:genetics; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics* / Q000378:metabolism; D016547:Kinesins / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000502:physiology; D051379:Mice; D009154:Mutation; D009473:Neuronal Plasticity / Q000235:genetics; D009474:Neurons / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D024642:Potassium Channels, Voltage-Gated / Q000502:physiology*; D017470:Receptors, Glutamate / Q000378:metabolism*; D013569:Synapses / Q000502:physiology
chemical_list: D029742:Caenorhabditis elegans Proteins; D024642:Potassium Channels, Voltage-Gated; D017470:Receptors, Glutamate; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; C517679:unc-43 protein, C elegans; D016547:Kinesins
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