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
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
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DOI：
10.1096/fj.08-123737
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发表时间：
2009-07-01
期刊：
影响因子：
4.8
通讯作者：
Nomura, Kazuya
中科院分区：
文献类型：
--
作者：
Dejima, Katsufumi;Murata, Daisuke;Nomura, Kazuya
尽管溶质载体35B1 （SLC35B1）在进化上是保守的，但其在后生动物中的功能尚不清楚。为了阐明其功能，我们研究了SLC35B1家族基因（HUT-1: UDP-Gal转运体同源物）在秀丽隐杆线虫中的发育作用。我们分离了该基因的缺失突变体，并对突变体和hut-1 rnai处理的蠕虫的表型进行了表征。GFP-HUT-1报告基因分析检测基因表达模式。我们还测试了几种核苷酸糖转运蛋白是否可以补偿hut-1缺陷。hut-1缺失突变体和RNAi蠕虫表现出幼虫生长缺陷和致死率，肠道形态被破坏。hut-1失活诱导慢性内质网（ER）应激，并且hut-1与参与未折叠蛋白反应信号传导的atf-6、pek-1和fire -1基因表现出遗传相互作用。HUT-1缺失动物内质网超微结构和内质网标记物分布表明，HUT-1是维持内质网结构所必需的。报告分析显示，HUT- 1是一种在组织中普遍表达的内质网蛋白，包括肠。突变体的致死性和内质网应激表型通过人类hut-1同源物UGTrel1得以恢复。这些结果表明，hut-1在秀丽隐杆线虫内质网的发育和维持中起着重要的作用。- dejima， K., Murata， D., Mizuguchi， S., Nomura, k.h, Gengyo-Ando， K., Mitani， S., Kamiyama， S., Nishihara， S., Nomura， K.人类溶质载体家族35成员B1 （udp -半乳糖转运蛋白相关蛋白1）的同源物参与了秀丽隐杆线虫内质网稳态的维持，对幼虫发育至关重要。财经杂志，23,2215-2225 （2009）
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, 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. FASEB J. 23, 2215-2225 (2009)