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

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

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2979-2990
Number of pages12
JournalMolecular biology of the cell
Volume20
Issue number12
DOIs
Publication statusPublished - 2009 Jun 15
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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