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Originally published as MBC in Press, 10.1091/mbc.E04-02-0108 on August 18, 2004

Vol. 15, Issue 11, 4818-4828, November 2004

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The Unfolded Protein Response Regulates Glutamate Receptor Export from the Endoplasmic Reticulum{boxd}

Jaegal Shim *, Tohru Umemura *, Erika Nothstein, and Christopher Rongo {dagger}

The Waksman Institute, Department of Genetics, Rutgers University, Piscataway, NJ 08854

Submitted February 6, 2004; Revised August 2, 2004; Accepted August 4, 2004
Monitoring Editor: Lawrence Goldstein

{alpha}-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamate receptors mediate the majority of excitatory signaling in the CNS, and the functional properties and subcellular fate of these receptors depend on receptor subunit composition. Subunit assembly is thought to occur in the endoplasmic reticulum (ER), although we are just beginning to understand the underlying mechanism. Here we examine the trafficking of Caenorhabditis elegans glutamate receptors through the ER. Our data indicate that neurons require signaling by the unfolded protein response (UPR) to move GLR-1, GLR-2, and GLR-5 subunits out of the ER and through the secretory pathway. In contrast, other neuronal transmembrane proteins do not require UPR signaling for ER exit. The requirement for the UPR pathway is cell type and age dependent: impairment for receptor trafficking increases as animals age and does not occur in all neurons. Expression of XBP-1, a component of the UPR pathway, is elevated in neurons during development. Our results suggest that UPR signaling is a critical step in neural function that is needed for glutamate receptor assembly and secretion.

Article published online ahead of print. Mol. Biol. Cell 10.1091/mbc.E04–02–0108. Article and publication date are available at www.molbiolcell.org/cgi/doi/10.1091/mbc.E04–02–0108.

{boxd} The online version of this article contains supplementary material accessible through http://www.molbiolcell.org.

* These authors contributed equally to this work.

{dagger} Corresponding author. E-mail address: rongo{at}waksman.rutgers.edu.




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