title: Differential requirement of unfolded protein response pathway for calreticulin expression in Caenorhabditis elegans.
abstract: Accumulation of unfolded proteins in the endoplasmic reticulum triggers the unfolded protein response (UPR) pathway, which increases the expression of chaperones to maintain the homeostasis. Calreticulin is a calcium-binding chaperone located in the lumen of endoplasmic reticulum (ER). Here we show that in response to a UPR inducing reagent, tunicamycin, the expression of calreticulin (crt-1) is specifically up-regulated in Caenorhabditis elegans. Tunicamycin (TM) induced expression of the crt-1 requires IRE-1 and XBP-1 but is ATF-6 and PEK-1 independent. Analysis of the crt-1 promoter reveals a putative XBP-1 binding site at the -284 to -278 bp region, which was shown to be necessary for TM-mediated induction. Genetic analysis of crt-1 mutants and mutants of UPR pathway genes show various degrees of developmental arrest upon TM treatment. Our results suggest that the TM-induced UPR pathway culminates in the up-regulation of crt-1, which protects the worm from deleterious accumulation of unfolded proteins in the ER. Knockdown of the crt-1, pdi-2, or pdi-3 increased the crt-1 expression, whereas knockdown of the hsp-3 or hsp-4 did not have any effect on crt-1 expression, indicating the existence of complex compensatory networks to cope up with ER stress.
authors.affiliation: Department of Life Science, Gwangju Institute of Science and Technology, 1 Oryong-Dong, Buk-Gu, Gwangju, Korea.
authors.forename: Dukgyu
authors.initials: D
authors.lastname: Lee
authors.forename: Gunasekaran
authors.initials: G
authors.lastname: Singaravelu
authors.forename: Byung-Jae
authors.initials: BJ
authors.lastname: Park
authors.forename: Joohong
authors.initials: J
authors.lastname: Ahnn
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D037282:Calreticulin / Q000235:genetics / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D025461:Feedback, Physiological; D005786:Gene Expression Regulation / Q000187:drug effects; D006360:Heat-Shock Proteins / Q000172:deficiency / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D011489:Protein Denaturation; D019704:Protein Disulfide-Isomerases / Q000172:deficiency / Q000378:metabolism; D017510:Protein Folding; D020218:Response Elements / Q000235:genetics; D014415:Tunicamycin / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D037282:Calreticulin; D006360:Heat-Shock Proteins; D014415:Tunicamycin; D019704:Protein Disulfide-Isomerases