Cooperation between engulfment receptors: the case of ABCA1 and MEGF10.

Cooperation between engulfment receptors: the case of ABCA1 and MEGF10.
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DOI:
10.1371/journal.pone.0000120
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发表时间:
2006-12-27
期刊:
影响因子:
3.7
通讯作者:
Chimini G
Chimini G
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Hamon Y;Trompier D;Ma Z;Venegas V;Pophillat M;Mignotte V;Zhou Z;Chimini G

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吞噬垂死细胞是吞噬作用的一种特殊形式,在整个进化过程中非常保守。在蠕虫中,它由两条平行的途径遗传控制,这两条途径在哺乳动物中仅部分重组。我们专注于CED-1定义的途径在哺乳动物系统中的重演。我们首先探索并验证了MEGF 10,一种与CED-1具有惊人结构相似性的新型受体,作为哺乳动物中真正的功能性直系同源物,并因此朝着分析相应途径的分子相互作用沿着发展。我们确定,在通过转染强制表达的系统中,MEGF 10功能可以通过ATP结合盒转运蛋白ABCA 1(CED-7的直系同源物)进行调节。事实上,无论是功能性或突变ABCA 1的共表达施加了反式显性的正或负调制MEGF 10依赖性吞噬。生物化学和生物物理方法的结合使用表明,这种功能合作依赖于这些受体与共同的合作伙伴,在我们的细胞系统中内源性表达的交替关联。我们提供了在哺乳动物中构建CED-1依赖性途径的第一个工作模型。
The engulfment of dying cells is a specialized form of phagocytosis that is extremely conserved across evolution. In the worm, it is genetically controlled by two parallel pathways, which are only partially reconstituted in mammals. We focused on the recapitulation of the CED-1 defined pathway in mammalian systems. We first explored and validated MEGF10, a novel receptor bearing striking structural similarities to CED-1, as a bona fide functional ortholog in mammals and hence progressed toward the analysis of molecular interactions along the corresponding pathway. We ascertained that, in a system of forced expression by transfection, MEGF10 function can be modulated by the ATP binding cassette transporter ABCA1, ortholog to CED-7. Indeed, the coexpression of either a functional or a mutant ABCA1 exerted a transdominant positive or negative modulation on the MEGF10-dependent engulfment. The combined use of biochemical and biophysical approaches indicated that this functional cooperation relies on the alternate association of these receptors with a common partner, endogenously expressed in our cell system. We provide the first working model structuring in mammals the CED-1 dependent pathway.
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