Mok Lee-Peng, Qin Tielin, Bardot Boris, LeComte Matthew, Homayouni Asal, Ahimou Francois, Wesley Cedric
Department of Microbiology and Molecular Genetics, 322 Stafford Hall, 95 Carrigan Drive, The University of Vermont, Burlington, VT 05405, USA.
BMC Dev Biol. 2005 Mar 10;5:6. doi: 10.1186/1471-213X-5-6.
Delta, Notch, and Scabrous often function together to make different cell types and refine tissue patterns during Drosophila development. Delta is known as the ligand that triggers Notch receptor activity. Scabrous is known to bind Notch and promote Notch activity in response to Delta. It is not known if Scabrous binds Delta or Delta has activity other than its activity as a ligand of Notch. It is very difficult to clearly determine this binding or activity in vivo as all Notch, Delta, and Scabrous activities are required simultaneously or successively in an inter-dependent manner.
Using Drosophila cultured cells we show that the full length Delta promotes accumulation of Daughterless protein, fringe RNA, and pangolin RNA in the absence of Scabrous or Notch. Scabrous binds Delta and suppresses this activity even though it increases the level of the Delta intracellular domain. We also show that Scabrous can promote Notch receptor activity, in the absence of Delta.
Delta has activity that is independent of its activity as a ligand of Notch. Scabrous suppresses this Delta activity. Scabrous also promotes Notch activity that is dependent on Delta's ligand activity. Thus, Notch, Delta, and Scabrous might function in complex combinatorial or mutually exclusive interactions during development. The data reported here will be of significant help in understanding these interactions in vivo.
在果蝇发育过程中,Delta、Notch和Scabrous通常共同发挥作用,以形成不同的细胞类型并优化组织模式。Delta是已知的触发Notch受体活性的配体。已知Scabrous可结合Notch并响应Delta促进Notch活性。目前尚不清楚Scabrous是否结合Delta,或者Delta是否具有除作为Notch配体之外的其他活性。由于Notch、Delta和Scabrous的所有活性都以相互依赖的方式同时或相继需要,因此很难在体内明确确定这种结合或活性。
利用果蝇培养细胞,我们发现全长Delta在没有Scabrous或Notch的情况下可促进无女儿蛋白、边缘RNA和穿山甲RNA的积累。Scabrous结合Delta并抑制这种活性,尽管它增加了Delta细胞内结构域的水平。我们还表明,在没有Delta的情况下,Scabrous可以促进Notch受体活性。
Delta具有独立于其作为Notch配体活性的活性。Scabrous抑制这种Delta活性。Scabrous还促进依赖于Delta配体活性的Notch活性。因此,Notch、Delta和Scabrous在发育过程中可能以复杂的组合或相互排斥的相互作用发挥作用。本文报道的数据将对理解体内这些相互作用有很大帮助。