Mechanisms of postsynaptic localization of AMPA-type glutamate receptors and their regulation during long-term potentiation

• Published in: Science signaling 2019-01, Vol.12 (562)
• Main Authors: Buonarati, Olivia R, Hammes, Erik A, Watson, Jake F, Greger, Ingo H, Hell, Johannes W
• Format: Article
• Language: English
• Subjects: Actinin; Anchoring; Animals; Brain; Critical components; Dendrites; Dendrites - metabolism; Dendrites - physiology; Endoplasmic reticulum; Endosomes; Exocytosis; Gloss; Glutamate receptors; Glutamic acid; Golgi apparatus; Humans; Ion channels; Kinases; Learning; Localization; Long-term depression; Long-term potentiation; Long-Term Potentiation - physiology; Memory; Molecular modelling; Neuroplasticity; Neurotransmission; Plastic foam; Positioning devices (machinery); Postsynaptic density proteins; Protein kinase; Protein Transport; Protein turnover; Proteins; Receptors; Receptors, AMPA - metabolism; Receptors, Glutamate - metabolism; Synapses - metabolism; Synapses - physiology; Synaptic plasticity; Synaptic Potentials - physiology; Synaptic transmission; Synaptic Transmission - physiology; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid; α-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors
• ISSN: 1945-0877; 1937-9145
• DOI: 10.1126/SCISIGNAL.AAR6889

l-Glutamate is the main excitatory neurotransmitter in the brain, with postsynaptic responses to its release predominantly mediated by AMPA-type glutamate receptors (AMPARs). A critical component of synaptic plasticity involves changes in the number of responding postsynaptic receptors, which are dynamically recruited to and anchored at postsynaptic sites. Emerging findings continue to shed new light on molecular mechanisms that mediate AMPAR postsynaptic trafficking and localization. Accordingly, unconventional secretory trafficking of AMPARs occurs in dendrites, from the endoplasmic reticulum (ER) through the ER-Golgi intermediary compartment directly to recycling endosomes, independent of the Golgi apparatus. Upon exocytosis, AMPARs diffuse in the plasma membrane to reach the postsynaptic site, where they are trapped to contribute to transmission. This trapping occurs through a combination of both intracellular interactions, such as TARP (transmembrane AMPAR regulatory protein) binding to α-actinin-stabilized PSD-95, and extracellular interactions through the receptor amino-terminal domain. These anchoring mechanisms may facilitate precise receptor positioning with respect to glutamate release sites to enable efficient synaptic transmission.