Bromine is an essential trace element for assembly of collagen IV scaffolds in tissue development and architecture.

Bromine is an essential trace element for assembly of collagen IV scaffolds in tissue development and architecture.
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DOI:
10.1016/j.cell.2014.05.009
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发表时间:
2014-06-05
期刊:
影响因子:
64.5
通讯作者:
Hudson BG
Hudson BG
中科院分区:
生物学1区
文献类型:
--
作者:
McCall AS;Cummings CF;Bhave G;Vanacore R;Page-McCaw A;Hudson BG

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溴以溴离子(Br−)形式普遍存在于动物体内,但没有已知的基本功能。在此,我们证明了Br−是过氧化物酶催化形成硫亚胺交联所需的辅因子,硫亚胺交联是一种对基底膜(BM)的胶原IV支架内发现的组织发育和结构至关重要的翻译后修饰。溴化物转化为次溴酸,形成一种溴锍离子中间体,它强烈地选择形成硫亚胺。饮食中的Br-缺乏是致命的果蝇,而Br-补充恢复活力,证明其生理需求。重要的是,Br-缺乏的苍蝇表型复制在过氧化物酶突变体中观察到的发育和BM缺陷,并表明Br-,胶原IV和过氧化物酶之间的功能连接。我们确定Br−是胶原IV内硫亚胺形成所必需的,这是BM组装和组织发育的关键事件。因此,溴是所有动物的必需微量元素,其缺乏可能与营养和吸烟相关疾病中观察到的BM改变有关。
Bromine is ubiquitously present in animals as ionic bromide (Br−) yet has no known essential function. Herein, we demonstrate that Br− is a required cofactor for peroxidasin-catalyzed formation of sulfilimine crosslinks, a post-translational modification essential for tissue development and architecture found within the collagen IV scaffold of basement membranes (BMs). Bromide, converted to hypobromous acid, forms a bromosulfonium-ion intermediate that energetically selects for sulfilimine formation. Dietary Br-deficiency is lethal in Drosophila while Br-replenishment restores viability, demonstrating its physiologic requirement. Importantly, Br-deficient flies phenocopy the developmental and BM defects observed in peroxidasin mutants and indicate a functional connection between Br−, collagen IV, and peroxidasin. We establish that Br− is required for sulfilimine formation within collagen IV, an event critical for BM assembly and tissue development. Thus, bromine is an essential trace element for all animals and its deficiency may be relevant to BM alterations observed in nutritional and smoking related disease.
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