Activity patterns govern synapse-specific AMPA receptor trafficking between deliverable and synaptic pools.
In single neurons, glutamatergic synapses receiving distinct afferent inputs may contain AMPA receptors (-Rs) with unique subunit compositions. However, the cellular mechanisms by which differential receptor transport achieves this synaptic diversity remain poorly understood. In lateral geniculate neurons, we show that retinogeniculate and corticogeniculate synapses have distinct AMPA-R subunit compositions. Under basal conditions at both synapses, GluR1-containing AMPA-Rs are transported from an anatomically defined reserve pool to a deliverable pool near the postsynaptic density (PSD), but further incorporate into the PSD or functional synaptic pool only at retinogeniculate synapses. Vision-dependent activity, stimulation mimicking retinal input, or activation of CaMKII or Ras signaling regulated forward GluR1 trafficking from the deliverable pool to the synaptic pool at both synapses, whereas Rap2 signals reverse GluR1 transport at retinogeniculate synapses. These findings suggest that synapse-specific AMPA-R delivery involves constitutive and activity-regulated transport steps between morphological pools, a mechanism that may extend to the site-specific delivery of other membrane protein complexes.
Kielland
Anders
A
Department of Pharmacology, University of Virginia, Charlottesville, VA 22908, USA.
Bochorishvili
Genrieta
G
Corson
James
J
Zhang
Lei
L
Rosin
Diane L
DL
Heggelund
Paul
P
Zhu
J Julius
JJ
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D005829:Geniculate Bodies / Q000166:cytology; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D016253:Microscopy, Immunoelectron / Q000379:methods; D008959:Models, Neurological; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques / Q000379:methods; D021122:Protein Subunits / Q000378:metabolism*; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D051381:Rats; D018091:Receptors, AMPA / Q000172:deficiency / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D018709:Statistics, Nonparametric; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014161:Transduction, Genetic / Q000379:methods; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D000779:Anesthetics, Local; D004791:Enzyme Inhibitors; D021122:Protein Subunits; D018091:Receptors, AMPA; D049452:Green Fluorescent Proteins; D013779:Tetrodotoxin; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D018631:ras Proteins