title: 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.
abstract: 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.
authors.affiliation: Department of Biology, Faculty of Sciences 33, Kyushu University, Fukuoka 812-8581, Japan.
authors.forename: Katsufumi
authors.initials: K
authors.lastname: Dejima
authors.forename: Daisuke
authors.initials: D
authors.lastname: Murata
authors.forename: Souhei
authors.initials: S
authors.lastname: Mizuguchi
authors.forename: Kazuko H
authors.initials: KH
authors.lastname: Nomura
authors.forename: Keiko
authors.initials: K
authors.lastname: Gengyo-Ando
authors.forename: Shohei
authors.initials: S
authors.lastname: Mitani
authors.forename: Shin
authors.initials: S
authors.lastname: Kamiyama
authors.forename: Shoko
authors.initials: S
authors.lastname: Nishihara
authors.forename: Kazuya
authors.initials: K
authors.lastname: Nomura
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000502:physiology*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006706:Homeostasis; D007814:Larva / Q000254:growth & development*; D009004:Monosaccharide Transport Proteins / Q000502:physiology*; D033704:Nucleotide Transport Proteins; D010641:Phenotype; D034741:RNA, Small Interfering / Q000494:pharmacology; D017384:Sequence Deletion; D000099237:UDP-Galactose Translocators
chemical_list: D009004:Monosaccharide Transport Proteins; D033704:Nucleotide Transport Proteins; D034741:RNA, Small Interfering; D000099237:UDP-Galactose Translocators