Dual role of the exocyst in AMPA receptor targeting and insertion into the postsynaptic membrane.
Intracellular membrane trafficking of glutamate receptors at excitatory synapses is critical for synaptic function. However, little is known about the specialized trafficking events occurring at the postsynaptic membrane. We have found that two components of the exocyst complex, Sec8 and Exo70, separately control synaptic targeting and insertion of AMPA-type glutamate receptors. Sec8 controls the directional movement of receptors towards synapses through PDZ-dependent interactions. In contrast, Exo70 mediates receptor insertion at the postsynaptic membrane, but it does not participate in receptor targeting. Thus, interference with Exo70 function accumulates AMPA receptors inside the spine, forming a complex physically associated, but not yet fused with the postsynaptic membrane. Electron microscopic analysis of these complexes indicates that Exo70 mediates AMPA receptor insertion directly within the postsynaptic density, rather than at extrasynaptic membranes. Therefore, we propose a molecular and anatomical model that dissects AMPA receptor sorting and synaptic delivery within the spine, and uncovers new functions of the exocyst at the postsynaptic membrane.
Gerges
Nashaat Z
NZ
Department of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109-0632, USA.
Backos
Donald S
DS
Rupasinghe
Chamila N
CN
Spaller
Mark R
MR
Esteban
José A
JA
D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000648:ultrastructure; D008561:Membrane Fusion; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology*; D051379:Mice; D009154:Mutation; D009474:Neurons / Q000502:physiology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D021381:Protein Transport; D051381:Rats; D018091:Receptors, AMPA / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism; D013570:Synaptic Membranes / Q000378:metabolism*; D009435:Synaptic Transmission; D013574:Synaptosomes / Q000378:metabolism; D033921:Vesicular Transport Proteins
D002352:Carrier Proteins; C502251:Exoc7 protein, mouse; D008565:Membrane Proteins; D018091:Receptors, AMPA; C489608:Sec8l1 protein, mouse; D033921:Vesicular Transport Proteins