Physiological aspects of HAF-4 and HAF-9, C.elegansABC transporters, which cause abnormal formation of lysosome-related organelle.

HAF-4 和 HAF-9、C.elegansABC 转运蛋白的生理方面，导致溶酶体相关细胞器的异常形成。

• 批准号: 19590066
• 负责人: OHASHI Ayako
• 金额: $ 4.58万
• 依托单位: Iwate Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2007
• 资助国家: 日本
• 起止时间: 2007 至 2009
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-19590066/
• 关键词: トランスポーター; オルガネラ; 生理機能; 線虫; グノム; 薬学; バイオテクノロジー; 遺伝学

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.

类TAP（TAPL ; ABCB 9）是一种定位于溶酶体中的半型ATP结合盒（ABC）转运蛋白，其通过蛋白质将肽从胞质溶胶转运到溶酶体。然而，这种转运蛋白的生理作用仍有待阐明。基因组数据库的比较表明，TAPL是保守的各种物种，从一个简单的模式生物，秀丽隐杆线虫，哺乳动物。秀丽隐杆线虫具有同源的TAPL基因：haf-4和haf-9。在这项研究中，我们研究了这两个基因的组织特异性表达，并分析了haf-4和haf-9的功能丧失突变体的表型，以阐明这些基因在体内的功能。绿色荧光蛋白（GFP）标记的HAF-4和HAF-9主要定位于非酸性但溶酶体相关膜蛋白同源物（LMP-1）阳性的肠颗粒膜上。突变体haf-4和haf-9在晚期幼虫和年轻的成年肠道细胞中表现出颗粒缺陷，与窝仔数减少，排便周期延长和生长缓慢有关。肠颗粒表型被拯救的GFP标记的野生型蛋白的过表达，但不是由ATP-未结合的形式的HAF-4。这些结果表明，两个ABC转运蛋白，HAF-4和HAF-9，与肠道颗粒形成和其他一些生理方面。

项目成果

Functional dissection of transmembrane domains of human TAP-like (ABCB9).

人类 TAP 样 (ABCB9) 跨膜结构域的功能解剖。

• 发表时间: 2008
• 期刊: Biochem Biophys Res Commun. 377
• 作者: Kamakura A;et al.
• 通讯作者: et al.

Role of the Caenorhabditis elegans ABC transporter genes in the biogenesis of intestinal lysosome-related organelle

秀丽隐杆线虫ABC转运蛋白基因在肠道溶酶体相关细胞器生物发生中的作用

• 发表时间: 2008
• 作者: Takahiro Tanji;Hirohisa Shiraishi;Yasuo Yoshida;Koujiro Tohyama;Mitsuo Yamada;Masatomo Maeda;Ayako Ohashi-Kobayashi
• 通讯作者: Ayako Ohashi-Kobayashi

線虫リソソーム関連輸送体の変異体に見られる腸内オルガネラ異常の解析～透過型電子顕微鏡を用いた超微細構造の観察～

线虫溶酶体相关转运蛋白突变体肠道细胞器异常分析~透射电子显微镜超微结构观察~

• 发表时间: 2008
• 作者: 白石博久;吉田康夫;丹治貴博;遠山稿二郎;大橋綾子
• 通讯作者: 大橋綾子

Functional dissection of transmembrane domains of human TAP-like (ABCB9) Biochem.

人类 TAP 样 (ABCB9) Biochem 跨膜结构域的功能解剖。

• 发表时间: 2008
• 期刊: Biophys.Res.Commun. 377
• 作者: Aya Kamakura;Yasuyuki Fujimoto;Yu Motohashi;Kazuaki Ohashi;Ayako Ohashi-Kobayashi;Masatomo Maeda
• 通讯作者: Masatomo Maeda

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子集的正常形成需要 ATP 结合盒转运蛋白 HAF-4 和 HAF-9，它们与人溶酶体肽转运蛋白 TAP 样高度同源

• 发表时间: 2009
• 期刊: Mol. Biol. Cell 20
• 作者: 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.
• 通讯作者: Maeda M.