Differential Requirement of Unfolded Protein Response Pathway for Calreticulin Expression in Caenorhabditis elegans

Department of Life Science,Bio-NURI, Hallym University,Okchondong, Chunchon200-702, KoreaAccumulation of unfolded proteins in the endoplasmic reticulum triggersthe unfolded protein response (UPR) pathway, which increases the ex-pression of chaperones to maintain the homeostasis. Calreticulin is acalcium-binding chaperone located in the lumen of endoplasmic reticulum(ER). Here we show that in response to a UPR inducing reagent,tunicamycin,theexpressionofcalreticulin(crt-1)isspecificallyup-regulatedin Caenorhabditis elegans. Tunicamycin (TM) induced expression of the crt-1requires IRE-1 and XBP-1 but is ATF-6 and PEK-1 independent. Analysis ofthe 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-mediatedinduction. Genetic analysis of crt-1 mutants and mutants of UPR pathwaygenes show various degrees of developmental arrest upon TM treatment.Our results suggest that the TM-induced UPR pathway culminates in theup-regulation of crt-1, which protects the worm from deleteriousaccumulation of unfolded proteins in the ER. Knockdown of the crt-1, pdi-2,orpdi-3increasedthecrt-1expression,whereasknockdownofthehsp-3orhsp-4 did not have any effect on crt-1 expression, indicating the existence ofcomplex compensatory networks to cope up with ER stress.