Interactions between NEEP21, GRIP1 and GluR2 regulate sorting and recycling of the glutamate receptor subunit GluR2

Steiner, Pascal; Alberi, Stefano; Kulangara, Karina; Yersin, Alexandre; Sarria, J. C.; Regulier, Etienne; Kasas, Sandor; Dietler, Giovanni; Muller, Dominique; Catsicas, Stefan; Hirling, Harald

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Title		Interactions between NEEP21, GRIP1 and GluR2 regulate sorting and recycling of the glutamate receptor subunit GluR2
Authors		Steiner, Pascal Alberi, Stefano Kulangara, Karina Yersin, Alexandre Sarria, J. C. Regulier, Etienne Kasas, Sandor Dietler, Giovanni Muller, Dominique Catsicas, Stefan Hirling, Harald show all authors [1 - 11]
Published in		EMBO Journal. 2005, vol. 24, no. 16, p. 2873-2884
Abstract		Trafficking of AMPA-type glutamate receptors (AMPAR) between endosomes and the postsynaptic plasma membrane of neurons plays a central role in the control of synaptic strength associated with learning and memory. The molecular mechanisms of its regulation remain poorly understood, however. Here we show by biochemical and atomic force microscopy analyses that NEEP21, a neuronal endosomal protein necessary for receptor recycling including AMPAR, is associated with the scaffolding protein GRIP1 and the AMPAR subunit GluR2. Moreover, the interaction between NEEP21 and GRIP1 is regulated by neuronal activity. Expression of a NEEP21 fragment containing the GRIP1-binding site decreases surface GluR2 levels and delays recycling of internalized GluR2, which accumulates in early endosomes and lysosomes. Infusion of this fragment into pyramidal neurons of hippocampal slices induces inward rectification of AMPAR-mediated synaptic responses, suggesting decreased GluR2 expression at synapses. These results indicate that NEEP21-GRIP1 binding is crucial for GluR2-AMPAR sorting through endosomes and their recruitment to the plasma membrane, providing a first molecular mechanism to differentially regulate AMPAR subunit cycling in internal compartments.
Keywords		Animals — Carrier Proteins/ metabolism — Cell Membrane/ metabolism — Chromatography, Gel — Electrophysiology — Endosomes/ metabolism — Fluorescent Antibody Technique — Gene Expression Regulation — Hippocampus/metabolism — Immunoprecipitation — Microscopy, Atomic Force — Nerve Tissue Proteins/ metabolism — Neurons/ metabolism — Protein Transport/physiology — Rats — Receptors, AMPA/ metabolism — Synapses/ metabolism
Identifiers		DOI: 10.1038/sj.emboj.7600755 PMID: 16037816
Full text		Article - Limited access to UNIGE Other version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1187940/pdf/7600755a.pdf
Structures		Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales
Citation (ISO format)		STEINER, Pascal et al. Interactions between NEEP21, GRIP1 and GluR2 regulate sorting and recycling of the glutamate receptor subunit GluR2. In: EMBO Journal, 2005, vol. 24, n° 16, p. 2873-2884. https://archive-ouverte.unige.ch/unige:10451