Kinesin-1 Regulates Synaptic Strength by Mediating the Delivery, Removal, and Redistribution of AMPA Receptors

• Published in: Neuron (Cambridge, Mass.) Mass.), 2013-12, Vol.80 (6), p.1421-1437
• Main Authors: Hoerndli, Frédéric J., Maxfield, Dane A., Brockie, Penelope J., Mellem, Jerry E., Jensen, Erica, Wang, Rui, Madsen, David M., Maricq, Andres V.
• Format: Article
• Language: English
• Subjects: Animals; Behavior; 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; Experiments; Glutamic Acid - pharmacology; Heat; Kinesin - genetics; Kinesin - physiology; Lasers; Membrane Potentials - drug effects; Membrane Potentials - physiology; Mutation; Neurons; Receptors, AMPA - drug effects; Receptors, AMPA - metabolism; Synaptic Transmission - physiology; Worms
• ISSN: 0896-6273; 1097-4199
• DOI: 10.1016/j.neuron.2013.10.050

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. [Display omitted] •AMPAR trafficking in defined neurons in C. elegans is given in vivo analysis•The kinesin-1 motor UNC-116/KIF5 mediates transport of AMPARs to and from synapses•In unc-116 mutants, glutamate-gated currents and behaviors are disrupted•Cell autonomous synaptic and transport defects can be rescued in adult mutants In this issue, using real-time in vivo imaging and electrophysiology, Hoerndli et al., demonstrate that UNC-116/kinesin-1 has an ongoing role in AMPA receptor transport. This motor-driven transport modifies synaptic strength by regulating the delivery, removal, and composition of synaptic AMPA receptors.