SMF-1, SMF-2 and SMF-3 DMT1 orthologues regulate and are regulated differentially by manganese levels in C. elegans.
SMF-1, SMF-2 and SMF-3 DMT1 orthologues regulate and are regulated differentially by manganese levels in C. elegans.
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DOI：
10.1371/journal.pone.0007792
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发表时间：
2009-11-18
期刊：
影响因子：
3.7
通讯作者：
Aschner M
中科院分区：
文献类型：
--
作者：
Au C;Benedetto A;Anderson J;Labrousse A;Erikson K;Ewbank JJ;Aschner M
锰（Mn）是一种重要的金属，在高浓度下会产生毒性作用，最终导致帕金森症。哺乳动物中Mn的主要转运蛋白是二价金属转运蛋白（DMT 1）。我们在这里的特点DMT 1样蛋白在线虫C。elegans，其调节Mn和铁（Fe）含量并受其调节。我们在C.秀丽线虫：SMF-1、SMF-2和SMF-3。所有这三种都可以在功能上替代S.啤酒。在蠕虫中，缺失smf-1或smf-3导致锰耐受性增加，而缺失smf-2导致锰敏感性增加。通过QRT-PCR测量的smf mRNA水平在低Mn暴露时上调，在高Mn暴露时下调。翻译GFP融合显示，SMF-1和SMF-3强烈定位于部分重叠的顶端区域的肠上皮细胞，这表明一个不同的作用，SMF-1和SMF-3锰营养摄入。相反，在咽缘上皮中检测到SMF-2，可能参与金属感应。对smf突变体中Mn暴露后金属含量的分析表明，SMF-3是正常Mn吸收所需的，而smf-1是必需的。较高的SMF-2 mRNA水平与较高的铁含量相关，支持SMF-2在铁摄取中的作用。在smf-1和smf-3，但不是在smf-2突变体，锰暴露增加导致铁水平下降，这表明这两种金属竞争运输SMF-2。最后，SMF-3在锰暴露后可逆性下调。总之，我们揭示了在两个相邻组织中3个DMT 1样转运蛋白的转录和翻译后调节的复杂相互作用，这些转运蛋白调节C.优雅
Manganese (Mn) is an essential metal that can exert toxic effects at high concentrations, eventually leading to Parkinsonism. A major transporter of Mn in mammals is the divalent-metal transporter (DMT1). We characterize here DMT1-like proteins in the nematode C. elegans, which regulate and are regulated by Mn and iron (Fe) content. We identified three new DMT1-like genes in C. elegans: smf-1, smf-2 and smf-3. All three can functionally substitute for loss of their yeast orthologues in S. cerevisiae. In the worm, deletion of smf-1 or smf-3 led to an increased Mn tolerance, while loss of smf-2 led to increased Mn sensitivity. smf mRNA levels measured by QRT-PCR were up-regulated upon low Mn and down-regulated upon high Mn exposures. Translational GFP-fusions revealed that SMF-1 and SMF-3 strongly localize to partially overlapping apical regions of the gut epithelium, suggesting a differential role for SMF-1 and SMF-3 in Mn nutritional intake. Conversely, SMF-2 was detected in the marginal pharyngeal epithelium, possibly involved in metal-sensing. Analysis of metal content upon Mn exposure in smf mutants revealed that SMF-3 is required for normal Mn uptake, while smf-1 was dispensable. Higher smf-2 mRNA levels correlated with higher Fe content, supporting a role for SMF-2 in Fe uptake. In smf-1 and smf-3 but not in smf-2 mutants, increased Mn exposure led to decreased Fe levels, suggesting that both metals compete for transport by SMF-2. Finally, SMF-3 was post-translationally and reversibly down-regulated following Mn-exposure. In sum, we unraveled a complex interplay of transcriptional and post-translational regulations of 3 DMT1-like transporters in two adjacent tissues, which regulate metal-content in C. elegans.
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影响因子：
10.4
作者：
Brown, Rebecca C;Lockwood, Alan H;Sonawane, Babasaheb R
通讯作者：
Sonawane, Babasaheb R
影响因子：
2.1
作者：
Dorman, DC;McManus, BE;Everitt, JI
通讯作者：
Everitt, JI
影响因子：
4.8
作者：
Cohen, A;Nelson, H;Nelson, N
通讯作者：
Nelson, N
影响因子：
20.3
作者：
Forbes, JR;Gros, P
通讯作者：
Gros, P
DOI：
10.1073/pnas.92.22.10089
发表时间：
1995-10-24
影响因子：
11.1
作者：
CELLIER, M;PRIVE, G;GROS, P
通讯作者：
GROS, P