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Subunit rules governing the sorting of internalized AMPA receptors in hippocampal neurons.
Neuron. 2004 Jul 22; 43(2):221-36.N

Abstract

Removal of synaptic AMPA receptors is important for synaptic depression. Here, we characterize the roles of individual subunits in the inducible redistribution of AMPA receptors from the cell surface to intracellular compartments in cultured hippocampal neurons. The intracellular accumulation of GluR2 and GluR3 but not GluR1 is enhanced by AMPA, NMDA, or synaptic activity. After AMPA-induced internalization, homomeric GluR2 enters the recycling pathway, but following NMDA, GluR2 is diverted to late endosomes/lysosomes. In contrast, GluR1 remains in the recycling pathway, and GluR3 is targeted to lysosomes regardless of NMDA receptor activation. Interaction with NSF plays a role in regulated lysosomal targeting of GluR2. GluR1/GluR2 heteromeric receptors behave like GluR2 homomers, and endogenous AMPA receptors show differential activity-dependent sorting similar to homomeric GluR2. Thus, GluR2 is a key subunit that controls recycling and degradation of AMPA receptors after internalization.

Authors+Show Affiliations

Lee SH
The Picower Center for Learning and Memory, Massachusetts Institute of Technology, Cambridge 02139, USA.
Simonetta A
No affiliation info available
Sheng M
No affiliation info available

MeSH

AnimalsCOS CellsCell MembraneCells, CulturedChlorocebus aethiopsCytoplasmEndocytosisExcitatory Amino Acid AgonistsHippocampusIntracellular MembranesLysosomesN-MethylaspartateNeuronsProtein IsoformsProtein Structure, TertiaryRNA, Small InterferingRatsRats, Sprague-DawleyReceptors, AMPASynapsesTissue Distributionalpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15260958

Citation

Lee, Sang Hyoung, et al. "Subunit Rules Governing the Sorting of Internalized AMPA Receptors in Hippocampal Neurons." Neuron, vol. 43, no. 2, 2004, pp. 221-36.
Lee SH, Simonetta A, Sheng M. Subunit rules governing the sorting of internalized AMPA receptors in hippocampal neurons. Neuron. 2004;43(2):221-36.
Lee, S. H., Simonetta, A., & Sheng, M. (2004). Subunit rules governing the sorting of internalized AMPA receptors in hippocampal neurons. Neuron, 43(2), 221-36.
Lee SH, Simonetta A, Sheng M. Subunit Rules Governing the Sorting of Internalized AMPA Receptors in Hippocampal Neurons. Neuron. 2004 Jul 22;43(2):221-36. PubMed PMID: 15260958.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Subunit rules governing the sorting of internalized AMPA receptors in hippocampal neurons. AU - Lee,Sang Hyoung, AU - Simonetta,Alyson, AU - Sheng,Morgan, PY - 2003/09/12/received PY - 2004/04/12/revised PY - 2004/06/12/accepted PY - 2004/7/21/pubmed PY - 2004/8/27/medline PY - 2004/7/21/entrez SP - 221 EP - 36 JF - Neuron JO - Neuron VL - 43 IS - 2 N2 - Removal of synaptic AMPA receptors is important for synaptic depression. Here, we characterize the roles of individual subunits in the inducible redistribution of AMPA receptors from the cell surface to intracellular compartments in cultured hippocampal neurons. The intracellular accumulation of GluR2 and GluR3 but not GluR1 is enhanced by AMPA, NMDA, or synaptic activity. After AMPA-induced internalization, homomeric GluR2 enters the recycling pathway, but following NMDA, GluR2 is diverted to late endosomes/lysosomes. In contrast, GluR1 remains in the recycling pathway, and GluR3 is targeted to lysosomes regardless of NMDA receptor activation. Interaction with NSF plays a role in regulated lysosomal targeting of GluR2. GluR1/GluR2 heteromeric receptors behave like GluR2 homomers, and endogenous AMPA receptors show differential activity-dependent sorting similar to homomeric GluR2. Thus, GluR2 is a key subunit that controls recycling and degradation of AMPA receptors after internalization. SN - 0896-6273 UR - https://www.unboundmedicine.com/medline/citation/15260958/Subunit_rules_governing_the_sorting_of_internalized_AMPA_receptors_in_hippocampal_neurons_ DB - PRIME DP - Unbound Medicine ER -