Drosophila Ninjurin A induces nonapoptotic cell death.

Drosophila Ninjurin A induces nonapoptotic cell death.
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DOI:
10.1371/journal.pone.0044567
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Page-McCaw A
Page-McCaw A
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Broderick S;Wang X;Simms N;Page-McCaw A

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忍伤蛋白是保守的跨膜蛋白,在不同物种中响应损伤和应激而上调。它们的生物学功能尚不清楚,部分原因是对其功能的体内研究很少。我们分析了三种果蝇 Ninjurin 之一 NijA 的表达和功能。我们发现,脓毒症损伤后,NijA 蛋白重新分布到幼虫免疫组织的细胞表面,并通过 Toll 途径上调。我们生成了 NijA 的无效突变体,它没有表现出可检测到的表型。在异位表达研究中,NijA 诱导细胞死亡,细胞损失和吖啶橙染色证明了这一点。这些垂死细胞没有表现出凋亡细胞的特征,包括 TUNEL 染色和 p35 抑制,表明 NijA 诱导非凋亡细胞死亡。在细胞培养中,NijA 还会诱导细胞死亡,这种死亡似乎是细胞自主的。这些体内研究确定了 Ninjurin 家族在诱导非凋亡细胞死亡中的新作用。
Ninjurins are conserved transmembrane proteins that are upregulated across species in response to injury and stress. Their biological functions are not understood, in part because there have been few in vivo studies of their function. We analyzed the expression and function of one of three Drosophila Ninjurins, NijA. We found that NijA protein is redistributed to the cell surface in larval immune tissues after septic injury and is upregulated by the Toll pathway. We generated a null mutant of NijA, which displayed no detectable phenotype. In ectopic expression studies, NijA induced cell death, as evidenced by cell loss and acridine orange staining. These dying cells did not display hallmarks of apoptotic cells including TUNEL staining and inhibition by p35, indicating that NijA induced nonapoptotic cell death. In cell culture, NijA also induced cell death, which appeared to be cell autonomous. These in vivo studies identify a new role for the Ninjurin family in inducing nonapoptotic cell death.
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