Centre d'Immunologie de Marseille Luminy, Institut National de la Santé et de la Recherche Médicale, Université de la Méditerranée, Marseille, France.
PLoS One. 2006 Dec 27;1(1):e120. doi: 10.1371/journal.pone.0000120.
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.
细胞吞噬是一种专门的吞噬形式，在进化过程中高度保守。在蠕虫中，它由两条平行的途径遗传控制，而这些途径在哺乳动物中只部分重建。我们专注于在哺乳动物系统中重现 CED-1 定义的途径。我们首先探索并验证了 MEGF10，这是一种新型受体，与 CED-1 具有惊人的结构相似性，是哺乳动物中真正的功能同源物，因此我们继续分析相应途径中的分子相互作用。我们确定，在转染的强制表达系统中，MEGF10 的功能可以通过 ABCA1 转运体（与 CED-7 同源）的 ATP 结合盒进行调节。事实上，功能性或突变型 ABCA1 的共表达对 MEGF10 依赖性吞噬作用产生了显性正或负调节作用。生化和生物物理方法的联合使用表明，这种功能合作依赖于这些受体与共同伴侣的交替结合，而该共同伴侣在我们的细胞系统中内源性表达。我们提供了第一个工作模型，在哺乳动物中构建了 CED-1 依赖的途径。
