Normal formation of a subset of intestinal granules in Caenorhabditis elegans requires ATP-binding cassette transporters HAF-4 and HAF-9, which are highly homologous to human lysosomal peptide transporter TAP-like

秀丽隐杆线虫肠道颗粒亚群的正常形成需要 ATP 结合盒转运蛋白 HAF-4 和 HAF-9,它们与人类溶酶体肽转运蛋白 TAP 样转运蛋白高度同源

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作者:Hiromi Kawai, Takahiro Tanji, Hirohisa Shiraishi, Mitsuo Yamada, Ryoko Iijima, Takao Inoue, Yasuko Kezuka, Kazuaki Ohashi, Yasuo Yoshida, Koujiro Tohyama, Keiko Gengyo-Ando, Shohei Mitani, Hiroyuki Arai, Ayako Ohashi-Kobayashi, Masatomo Maeda

Abstract

TAP-like (TAPL; ABCB9) is a half-type ATP-binding cassette (ABC) transporter that localizes in lysosome and putatively conveys peptides from cytosol to lysosome. However, the physiological role of this transporter remains to be elucidated. Comparison of genome databases reveals that TAPL is conserved in various species from a simple model organism, Caenorhabditis elegans, to mammals. C. elegans possesses homologous TAPL genes: haf-4 and haf-9. In this study, we examined the tissue-specific expression of these two genes and analyzed the phenotypes of the loss-of-function mutants for haf-4 and haf-9 to elucidate the in vivo function of these genes. Both HAF-4 and HAF-9 tagged with green fluorescent protein (GFP) were mainly localized on the membrane of nonacidic but lysosome-associated membrane protein homologue (LMP-1)-positive intestinal granules from larval to adult stage. The mutants for haf-4 and haf-9 exhibited granular defects in late larval and young adult intestinal cells, associated with decreased brood size, prolonged defecation cycle, and slow growth. The intestinal granular phenotype was rescued by the overexpression of the GFP-tagged wild-type protein, but not by the ATP-unbound form of HAF-4. These results demonstrate that two ABC transporters, HAF-4 and HAF-9, are related to intestinal granular formation and some other physiological aspects.

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