AMPA receptors commandeer an ancient cargo exporter for use as an auxiliary subunit for signaling.

Fast excitatory neurotransmission in the mammalian central nervous system is mainly mediated by ionotropic glutamate receptors of the AMPA subtype (AMPARs). AMPARs are protein complexes of the pore-lining α-subunits GluA1-4 and auxiliary β-subunits modulating their trafficking and gating. By a prote...

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Autores principales:	Nadine Harmel, Barbara Cokic, Gerd Zolles, Henrike Berkefeld, Veronika Mauric, Bernd Fakler, Valentin Stein, Nikolaj Klöcker
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3995b600a67b43d9a7d4337429c02548
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spelling	oai:doaj.org-article:3995b600a67b43d9a7d4337429c025482021-11-18T07:29:26ZAMPA receptors commandeer an ancient cargo exporter for use as an auxiliary subunit for signaling.1932-620310.1371/journal.pone.0030681https://doaj.org/article/3995b600a67b43d9a7d4337429c025482012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22292017/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Fast excitatory neurotransmission in the mammalian central nervous system is mainly mediated by ionotropic glutamate receptors of the AMPA subtype (AMPARs). AMPARs are protein complexes of the pore-lining α-subunits GluA1-4 and auxiliary β-subunits modulating their trafficking and gating. By a proteomic approach, two homologues of the cargo exporter cornichon, CNIH-2 and CNIH-3, have recently been identified as constituents of native AMPARs in mammalian brain. In heterologous reconstitution experiments, CNIH-2 promotes surface expression of GluAs and modulates their biophysical properties. However, its relevance in native AMPAR physiology remains controversial. Here, we have studied the role of CNIH-2 in GluA processing both in heterologous cells and primary rat neurons. Our data demonstrate that CNIH-2 serves an evolutionarily conserved role as a cargo exporter from the endoplasmic reticulum (ER). CNIH-2 cycles continuously between ER and Golgi complex to pick up cargo protein in the ER and then to mediate its preferential export in a coat protein complex (COP) II dependent manner. Interaction with GluA subunits breaks with this ancestral role of CNIH-2 confined to the early secretory pathway. While still taking advantage of being exported preferentially from the ER, GluAs recruit CNIH-2 to the cell surface. Thus, mammalian AMPARs commandeer CNIH-2 for use as a bona fide auxiliary subunit that is able to modify receptor signaling.Nadine HarmelBarbara CokicGerd ZollesHenrike BerkefeldVeronika MauricBernd FaklerValentin SteinNikolaj KlöckerPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 1, p e30681 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Nadine Harmel Barbara Cokic Gerd Zolles Henrike Berkefeld Veronika Mauric Bernd Fakler Valentin Stein Nikolaj Klöcker AMPA receptors commandeer an ancient cargo exporter for use as an auxiliary subunit for signaling.
description	Fast excitatory neurotransmission in the mammalian central nervous system is mainly mediated by ionotropic glutamate receptors of the AMPA subtype (AMPARs). AMPARs are protein complexes of the pore-lining α-subunits GluA1-4 and auxiliary β-subunits modulating their trafficking and gating. By a proteomic approach, two homologues of the cargo exporter cornichon, CNIH-2 and CNIH-3, have recently been identified as constituents of native AMPARs in mammalian brain. In heterologous reconstitution experiments, CNIH-2 promotes surface expression of GluAs and modulates their biophysical properties. However, its relevance in native AMPAR physiology remains controversial. Here, we have studied the role of CNIH-2 in GluA processing both in heterologous cells and primary rat neurons. Our data demonstrate that CNIH-2 serves an evolutionarily conserved role as a cargo exporter from the endoplasmic reticulum (ER). CNIH-2 cycles continuously between ER and Golgi complex to pick up cargo protein in the ER and then to mediate its preferential export in a coat protein complex (COP) II dependent manner. Interaction with GluA subunits breaks with this ancestral role of CNIH-2 confined to the early secretory pathway. While still taking advantage of being exported preferentially from the ER, GluAs recruit CNIH-2 to the cell surface. Thus, mammalian AMPARs commandeer CNIH-2 for use as a bona fide auxiliary subunit that is able to modify receptor signaling.
format	article
author	Nadine Harmel Barbara Cokic Gerd Zolles Henrike Berkefeld Veronika Mauric Bernd Fakler Valentin Stein Nikolaj Klöcker
author_facet	Nadine Harmel Barbara Cokic Gerd Zolles Henrike Berkefeld Veronika Mauric Bernd Fakler Valentin Stein Nikolaj Klöcker
author_sort	Nadine Harmel
title	AMPA receptors commandeer an ancient cargo exporter for use as an auxiliary subunit for signaling.
title_short	AMPA receptors commandeer an ancient cargo exporter for use as an auxiliary subunit for signaling.
title_full	AMPA receptors commandeer an ancient cargo exporter for use as an auxiliary subunit for signaling.
title_fullStr	AMPA receptors commandeer an ancient cargo exporter for use as an auxiliary subunit for signaling.
title_full_unstemmed	AMPA receptors commandeer an ancient cargo exporter for use as an auxiliary subunit for signaling.
title_sort	ampa receptors commandeer an ancient cargo exporter for use as an auxiliary subunit for signaling.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/3995b600a67b43d9a7d4337429c02548
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AMPA receptors commandeer an ancient cargo exporter for use as an auxiliary subunit for signaling.

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