2009 Fiscal Year Final Research Report
Physiological aspects of HAF-4 and HAF-9, C.elegansABC transporters, which cause abnormal formation of lysosome-related organelle.
| Project/Area Number |
19590066
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Iwate Medical University |
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Principal Investigator |
OHASHI Ayako (小林 綾子) Iwate Medical University, 薬学部, 教授 (90272484)
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| Co-Investigator(Renkei-kenkyūsha) |
SHIRAISHI Hirohisa 岩手医科大学, 薬学部, 講師 (80393156)
TANJI Takahiro 岩手医科大学, 薬学部, 助教 (60453320)
NISHIKORI Kenji 岩手医科大学, 薬学部, 助手 (20563844)
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| Project Period (FY) |
2007 – 2009
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| Keywords | トランスポーター / オルガネラ / 生理機能 / 線虫 |
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| Research 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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[Journal Article] 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-like2009
Author(s)
Kawai H., Tanji T., Shiraishi H., Yamada M., Iijima R., Inoue T., Kezuka Y., Ohashi K., Yoshida Y., Tohyama K., Gengyo-Ando K., Mitani S., Arai H., Ohashi-Kobayashi A., Maeda M.
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Journal Title
Mol. Biol. Cell 20
Pages: 2979-2990
Peer Reviewed
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