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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
Author(s) -
Dejima Katsufumi,
Murata Daisuke,
Mizuguchi Souhei,
Nomura Kazuko H.,
Gengyo-Ando Keiko,
Mitani Shohei,
Kamiyama Shin,
Nishihara Shoko,
Nomura Kazuya
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-123737
Subject(s) - caenorhabditis elegans , unfolded protein response , biology , endoplasmic reticulum , mutant , rna interference , microbiology and biotechnology , phenotype , gene , genetic screen , mutation , genetics , rna
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 RNAitreated 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, K.,Murata, D., Mizuguchi, S., Nomura, K. H., Gengyo‐Ando, K.,Mitani, S., Kamiyama, S., Nishihara, S., Nomura, K. 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 . FASEBJ. 23, 2215–2225 (2009)