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The ortholog of human solute carrier family 35 member B1 (UDP-galactose transporter-related protein 1) is involved in maintenance of ER homeostasis and essential for larval development in Caenorhabditis elegans

Katsufumi Dejima^*,, Daisuke Murata^*,, Souhei Mizuguchi^*,, Kazuko H. Nomura^*,, Keiko Gengyo-Ando^,, Shohei Mitani^,, Shin Kamiyama, Shoko Nishihara^, and Kazuya Nomura^*,,1

^* Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka, Japan;

Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama, Japan;

Department of Physiology, Tokyo Women’s Medical University School of Medicine, Tokyo, Japan; and

Department of Bioinformatics, Laboratory of Cell Biology, Faculty of Engineering, Soka University, Tokyo, Japan

¹ Correspondence: Department of Biology, Faculty of Sciences 33, Kyushu University, Fukuoka 812-8581, Japan. E-mail: knomuscb{at}mbox.kyushu-u.ac.jp

Although the solute carrier 35B1 (SLC35B1) is evolutionarily conserved, its functions in metazoans remain unknown. To elucidate its function, we examined developmental roles of an SLC35B1 family gene (HUT-1: homolog of UDP-Gal transporter) in Caenorhabditis elegans. We isolated a deletion mutant of the gene and characterized phenotypes of the mutant and hut-1 RNAi-treated worms. GFP-HUT-1 reporter analysis was performed to examine gene expression patterns. We also tested whether several nucleotide sugar transporters can compensate for hut-1 deficiency. The hut-1 deletion mutant and RNAi worms showed larval growth defect and lethality with disrupted intestinal morphology. Inactivation of hut-1 induced chronic endoplasmic reticulum (ER) stress, and hut-1 showed genetic interactions with the atf-6, pek-1, and ire-1 genes involved in unfolded protein response signaling. ER ultrastructure and ER marker distribution in hut-1-deficient animals showed that HUT-1 is required for maintenance of ER structure. Reporter analysis revealed that HUT-1 is an ER protein ubiquitously expressed in tissues, including the intestine. Lethality and the ER stress phenotype of the mutant were rescued with the human hut-1 ortholog UGTrel1. These results indicate important roles for hut-1 in development and maintenance of ER homeostasis in C. elegans.

Key Words: ER stress • RNAi • deletion mutant • glycosylation • model organism