Complex proteolytic processing acts on Delta, a transmembrane ligand for notch, during Drosophila development

Complex proteolytic processing acts on Delta, a transmembrane ligand for notch, during Drosophila development
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DOI:
10.1091/mbc.9.7.1709
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发表时间:
1998-07-01
影响因子:
3.3
通讯作者:
Muskavitch, MAT
Muskavitch, MAT
中科院分区:
生物学3区
文献类型:
--
作者:
Klueg, KM;Parody, TR;Muskavitch, MAT

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Delta作为细胞非自主性膜结合配体,在细胞命运指定期间与Notch(细胞自主性受体)结合。Delta和Notch之间的相互作用导致信号传导和引发细胞反应。在我们的调查,以进一步了解Delta信号调节的生化机制,我们已经确定了果蝇胚胎和幼虫提取物中的四个Delta亚型。我们已经证明,至少有一个较小的亚型,δ S,从蛋白水解的结果。在共定位实验中使用针对Delta细胞外和细胞内结构域的抗体,我们发现至少有三种Delta同种型存在于体内,这提供了在发育过程中存在多种形式Delta的第一个证据。最后,我们证明了Delta是一种跨膜配体,可以被表达Notch的果蝇培养细胞吸收。细胞培养实验暗示全长Delta被表达Notch的细胞摄取。我们目前的证据表明,这种吸收发生的非吞噬机制。
Delta functions as a cell nonautonomous membrane-bound ligand that binds to Notch, a cell-autonomous receptor, during cell fate specification. Interaction between Delta and Notch leads to signal transduction and elicitation of cellular responses. During our investigations to further understand the biochemical mechanism by which Delta signaling is regulated, we have identified four Delta isoforms in Drosophila embryonic and larval extracts. We have demonstrated that at least one of the smaller isoforms, Delta S, results from proteolysis. Using antibodies to the Delta extracellular and intracellular domains in colocalization experiments, we have found that at least three Delta isoforms exist in vivo, providing the first evidence that multiple forms of Delta exist during development. Finally, we demonstrate that Delta is a transmembrane ligand that can be taken up by Notch-expressing Drosophila cultured cells. Cell culture experiments imply that full-length Delta is taken up by Notch-expressing cells. We present evidence that suggests this uptake occurs by a nonphagocytic mechanism.