Agonist Occupancy Is Essential for Forward Trafficking of AMPA Receptors

Coleman, Sarah K.; Möykkynen, Tommi; Jouppila, Annukka; Koskelainen, Susanna; Rivera, Claudio; Korpi, Esa R.; Keinänen, Kari

doi:10.1523/jneurosci.3953-08.2009

Cited by 35 publications

(48 citation statements)

References 56 publications

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“…Recent work on the biosynthesis of AMPARs may provide some insight into the second question. It has been proposed that during AMPAR biosynthesis, glutamate-induced conformational changes in the ER serve as early trafficking checkpoints to ensure that only functional receptors are exported to the cell surface (23)(24)(25)(26)(27). It may be a common function of CNIHs and TARPs to participate in glutamate-induced conformational changes by immature AMPARs, which then disengage from CNIHs but remain bound to TARPs as they are delivered to the plasma membrane and then targeted to synapses.…”

Section: Discussionmentioning

confidence: 99%

Functional comparison of the effects of TARPs and cornichons on AMPA receptor trafficking and gating

Shi¹,

Suh

Milstein

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

110

159

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Glutamate receptors of the AMPA subtype (AMPARs) mediate fast synaptic transmission in the brain. These ionotropic receptors rely on auxiliary subunits known as transmembrane AMPAR regulatory proteins (TARPs) for both trafficking and gating. Recently, a second family of AMPAR binding proteins, referred to as cornichons, were identified and also proposed to function as auxiliary subunits. Cornichons are transmembrane proteins that modulate AMPAR function in expression systems much like TARPs. In the present study we compare the role of cornichons in controlling AMPA receptor function in neurons and HEK cells to that of TARPs. Cornichons mimic some, but not all, of the actions of TARPs in HEK cells; their role in neurons, however, is more limited. Although expressed cornichons can affect the trafficking of AMPARs, they were not detected on the surface of neurons and failed to alter the kinetics of endogenous AMPARs. This neuronal role is more consistent with that of an endoplasmic reticulum (ER) chaperone rather than a bona fide auxiliary subunit.stargazin | synapse | auxiliary subunit | hippocampus

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Section: Discussionmentioning

confidence: 99%

Functional comparison of the effects of TARPs and cornichons on AMPA receptor trafficking and gating

Shi¹,

Suh

Milstein

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

110

159

View full text Add to dashboard Cite

show abstract

“…SDS-PAGE, immunoblotting, and cell surface biotinylation were carried out essentially as described previously (27,32). The glycosylation status of receptor subunits was analyzed by determining the accessibility of N-glycans to endo-␤-N-acetylglucosaminidase H (endo H, New England Biolabs, catalog no.…”

Section: Methodsmentioning

confidence: 99%

The N-terminal Domain Modulates α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) Receptor Desensitization

Möykkynen

Coleman

Semenov

et al. 2014

Journal of Biological Chemistry

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“…Since the TM2-TM3 linker is located close to the transmembrane allosteric site (Hibbs and Gouaux, 2011), such a Tyr83 contact may promote gating of the ion channel, resulting in higher current amplitude of the IVM response. Alternatively, the stabilized open conformation may accelerate exit from the ER, thereby enhancing the number of functional BmGluCls as in the case of ionotropic L-glutamategated cation channels (Fleck, 2006;Penn et al, 2008;Coleman et al, 2009;Gill et al, 2009).…”

Section: Structural Features Influencing Glucl Numbers In Membranesmentioning

confidence: 99%

Exon 3 Splicing and Mutagenesis Identify Residues Influencing Cell Surface Density of Heterologously Expressed Silkworm (Bombyx mori) Glutamate-Gated Chloride Channels

et al. 2014

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Glutamate-gated chloride channels (GluCls) mediate fast inhibitory neurotransmission in invertebrate nervous systems. Insect GluCls show alternative splicing, and, to determine its impact on channel function and pharmacology, we isolated GluCl cDNAs from larvae of the silkworm (Bombyx mori). We show that six B. mori glutamategated chloride channel variants are generated by splicing in exons 3 and 9 and that exons 3b and 3c are common in the brain and third thoracic ganglion. When expressed in Xenopus laevis oocytes, the three functional exon 3 variants (3a, b, c) all had similar EC 50 values for L-glutamate and ivermectin (IVM); however, I max (the maximum L-glutamate-and IVM-induced response of the channels at saturating concentrations) differed strikingly between variants, with the 3c variant showing the largest L-glutamate-and IVM-induced responses. By contrast, a partial deletion detected in exon 9 had a much smaller impact on L-glutamate and IVM actions. Binding assays using [ Modeling the GluCl 3a and 3c variants suggested that three of the four amino acids contribute to intersubunit contacts, whereas the other interacts with the TM2-TM3 linker, influencing the receptor response.

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Agonist Occupancy Is Essential for Forward Trafficking of AMPA Receptors

Cited by 35 publications

References 56 publications

Functional comparison of the effects of TARPs and cornichons on AMPA receptor trafficking and gating

Functional comparison of the effects of TARPs and cornichons on AMPA receptor trafficking and gating

The N-terminal Domain Modulates α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) Receptor Desensitization

Exon 3 Splicing and Mutagenesis Identify Residues Influencing Cell Surface Density of Heterologously Expressed Silkworm (Bombyx mori) Glutamate-Gated Chloride Channels

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