Kinesin-1 regulates synaptic strength by mediating the delivery, removal, and redistribution of AMPA receptors

Neuron. 2013 Dec 18;80(6):1421-37. doi: 10.1016/j.neuron.2013.10.050.

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.

Publication types

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

MeSH terms

  • Animals
  • Caenorhabditis elegans Proteins / drug effects
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Caenorhabditis elegans Proteins / physiology*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology*
  • Cycloheximide / pharmacology
  • Glutamic Acid / pharmacology
  • Kinesin / genetics
  • Kinesin / physiology*
  • Membrane Potentials / drug effects
  • Membrane Potentials / physiology
  • Mutation
  • Receptors, AMPA / drug effects
  • Receptors, AMPA / metabolism*
  • Synaptic Transmission / physiology*

Substances

  • Caenorhabditis elegans Proteins
  • Cell Cycle Proteins
  • GLR-2 protein, C elegans
  • Receptors, AMPA
  • UNC-116 protein, C elegans
  • glr-1 protein, C elegans
  • Glutamic Acid
  • Cycloheximide
  • KLP-4 protein, C elegans
  • Kinesin