A systematic screen for dominant second-site modifiers of Merlin/NF2 phenotypes reveals an interaction with blistered/DSRF and scribbler.
A systematic screen for dominant second-site modifiers of Merlin/NF2 phenotypes reveals an interaction with blistered/DSRF and scribbler.
复制标题
DOI：
--
复制
发表时间：
2001-06
期刊：
影响因子：
3.3
通讯作者：
Dennis R. LaJeunesse;Brooke M. McCartney;R. Fehon
中科院分区：
文献类型：
--
作者：
Dennis R. LaJeunesse;Brooke M. McCartney;R. Fehon
Merlin是人类肿瘤抑制基因神经纤维瘤病2（NF 2）的果蝇同源物，是调节细胞增殖和分化所必需的。为了更好地了解NF 2基因产物Merlin的细胞功能，最近的工作集中在鉴定与其物理或功能相互作用的蛋白质上。在这篇文章中，我们描述了遗传筛选设计隔离梅林表型，我们已经确定了五个多等位基因互补组，修改功能丧失和显性阴性梅林表型的第二个网站修改器。其中三组，IIa组/scribbler（也称为无制动），IIc组/birbred和IId组/net，是已知的基因，而两个似乎是新的。此外，两个基因，组IIa/scribbler和组IIc/bischerred，改变梅林在上皮和神经元组织中的亚细胞定位，表明它们调节梅林运输或功能。此外，我们表明，在scribbler和bestarred显示第二个网站的非互补突变与彼此。这些结果表明，Merlin，besterred和scribbler功能在一个共同的途径来调节果蝇翅上皮发育。
Merlin, the Drosophila homologue of the human tumor suppressor gene Neurofibromatosis 2 (NF2), is required for the regulation of cell proliferation and differentiation. To better understand the cellular functions of the NF2 gene product, Merlin, recent work has concentrated on identifying proteins with which it interacts either physically or functionally. In this article, we describe genetic screens designed to isolate second-site modifiers of Merlin phenotypes from which we have identified five multiallelic complementation groups that modify both loss-of-function and dominant-negative Merlin phenotypes. Three of these groups, Group IIa/scribbler (also known as brakeless), Group IIc/blistered, and Group IId/net, are known genes, while two appear to be novel. In addition, two genes, Group IIa/scribbler and Group IIc/blistered, alter Merlin subcellular localization in epithelial and neuronal tissues, suggesting that they regulate Merlin trafficking or function. Furthermore, we show that mutations in scribbler and blistered display second-site noncomplementation with one another. These results suggest that Merlin, blistered, and scribbler function together in a common pathway to regulate Drosophila wing epithelial development.