title: Kinesin-1 regulates synaptic strength by mediating the delivery, removal, and redistribution of AMPA receptors.
abstract: A primary determinant of the strength of neurotransmission is the number of AMPA-type glutamate receptors (AMPARs) at synapses. However, we still lack a mechanistic understanding of how the number of synaptic AMPARs is regulated. Here, we show that UNC-116, the C. elegans homolog of vertebrate kinesin-1 heavy chain (KIF5), modifies synaptic strength by mediating the rapid delivery, removal, and redistribution of synaptic AMPARs. Furthermore, by studying the real-time transport of C. elegans AMPAR subunits in vivo, we demonstrate that although homomeric GLR-1 AMPARs can diffuse to and accumulate at synapses in unc-116 mutants, glutamate-gated currents are diminished because heteromeric GLR-1/GLR-2 receptors do not reach synapses in the absence of UNC-116/KIF5-mediated transport. Our data support a model in which ongoing motor-driven delivery and removal of AMPARs controls not only the number but also the composition of synaptic AMPARs, and thus the strength of synaptic transmission.
authors.affiliation: Department of Biology, Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Frédéric J
authors.initials: FJ
authors.lastname: Hoerndli
authors.affiliation: Department of Biology, Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Dane A
authors.initials: DA
authors.lastname: Maxfield
authors.affiliation: Department of Biology, Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Penelope J
authors.initials: PJ
authors.lastname: Brockie
authors.affiliation: Department of Biology, Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Jerry E
authors.initials: JE
authors.lastname: Mellem
authors.affiliation: Department of Biology, Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Erica
authors.initials: E
authors.lastname: Jensen
authors.affiliation: Department of Biology, Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Biology, Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Madsen
authors.affiliation: Department of Biology, Center for Cell and Genome Science, University of Utah, Salt Lake City, UT 84112, USA. Electronic address: maricq@biology.utah.edu.
authors.forename: Andres V
authors.initials: AV
authors.lastname: Maricq
mesh_terms: D000818:Animals; D029742:Caenorhabditis elegans Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D003513:Cycloheximide / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D016547:Kinesins / Q000235:genetics / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009154:Mutation; D018091:Receptors, AMPA / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; C498865:GLR-2 protein, C elegans; D018091:Receptors, AMPA; C502663:UNC-116 protein, C elegans; C096470:glr-1 protein, C elegans; D018698:Glutamic Acid; D003513:Cycloheximide; C578567:KLP-4 protein, C elegans; D016547:Kinesins