Differential requirement of unfolded protein response pathway for calreticulin expression in Caenorhabditis elegans.
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.
Lee
Dukgyu
D
Department of Life Science, Gwangju Institute of Science and Technology, 1 Oryong-Dong, Buk-Gu, Gwangju, Korea.
Singaravelu
Gunasekaran
G
Park
Byung-Jae
BJ
Ahnn
Joohong
J
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
D037282:Calreticulin; D006360:Heat-Shock Proteins; D014415:Tunicamycin; D019704:Protein Disulfide-Isomerases