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.
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.
Dejima
Katsufumi
K
Department of Biology, Faculty of Sciences 33, Kyushu University, Fukuoka 812-8581, Japan.
Murata
Daisuke
D
Mizuguchi
Souhei
S
Nomura
Kazuko H
KH
Gengyo-Ando
Keiko
K
Mitani
Shohei
S
Kamiyama
Shin
S
Nishihara
Shoko
S
Nomura
Kazuya
K
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
D009004:Monosaccharide Transport Proteins; D033704:Nucleotide Transport Proteins; D034741:RNA, Small Interfering; D000099237:UDP-Galactose Translocators