The unfolded protein response regulates glutamate receptor export from the endoplasmic reticulum.
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.
The Waksman Institute, Department of Genetics, Rutgers University, Piscataway, NJ 08854, USA.
Jaegal
J
Shim
Tohru
T
Umemura
Erika
E
Nothstein
Christopher
C
Rongo
D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008856:Microscopy, Fluorescence; D008954:Models, Biological; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D017510:Protein Folding; D021381:Protein Transport; D012313:RNA / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism; D017470:Receptors, Glutamate / Q000737:chemistry* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013997:Time Factors; D019076:Transgenes; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology*
D029742:Caenorhabditis elegans Proteins; D018076:DNA, Complementary; D018690:Excitatory Amino Acid Agonists; C498866:GLR-5 protein, C elegans; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; C096470:glr-1 protein, C elegans; D049452:Green Fluorescent Proteins; D012313:RNA; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid