Scribble protein domain mapping reveals a multistep localization mechanism and domains necessary for establishing cortical polarity
Scribble protein domain mapping reveals a multistep localization mechanism and domains necessary for establishing cortical polarity
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DOI：
10.1242/jcs.01525
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发表时间：
2004-12-01
影响因子：
4
通讯作者：
Doe, CQ
中科院分区：
文献类型：
--
作者：
Albertson, R;Chabu, C;Doe, CQ
果蝇肿瘤抑制蛋白Scribble是上皮细胞极性、成神经细胞极性、成神经细胞纺锤体不对称性和限制细胞增殖所必需的。它是一个新描述的蛋白质家族的成员，包含16个富含亮氨酸的重复序列（LRR），四个PDZ结构域和一个广泛的羧基末端（CT）结构域。LRR和PDZ结构域介导蛋白质-蛋白质相互作用，但对它们在蛋白质家族中的功能知之甚少。我们已经确定了LRR、PDZ和CT结构域对于成神经细胞和上皮细胞中Scribble定位以及成神经细胞中Scribble功能的作用。我们发现，LRR和PDZ结构域都需要适当的靶向的涂鸦分隔连接上皮细胞，LRR结构域是必要的和足够的皮质定位在有丝分裂成神经细胞，和PDZ 2结构域是需要有效的皮质和顶端定位的涂鸦在成神经细胞。此外，我们发现LRR结构域足以将米兰达蛋白靶向神经母细胞皮层，但LRR+PDZ将从皮层中排除米兰达。我们的研究结果突出了LRR和PDZ结构域在神经母细胞中的正确定位和功能的重要性。
The Drosophila tumor suppressor protein Scribble is required for epithelial polarity, neuroblast polarity, neuroblast spindle asymmetry and limiting cell proliferation. It is a member of the newly described LAP protein family, containing 16 leucine rich repeats (LRRs), four PDZ domains and an extensive carboxyl-terminal (CT) domain. LRR and PDZ domains mediate protein-protein interactions, but little is know about their function within LAP family proteins. We have determined the role of the LRR, PDZ and CT domains for Scribble localization in neuroblasts and epithelia, and for Scribble function in neuroblasts. We found that the LRR and PDZ domains are both required for proper targeting of Scribble to septate junctions in epithelia; that the LRR domain is necessary and sufficient for cortical localization in mitotic neuroblasts, and that the PDZ2 domain is required for efficient cortical and apical localization of Scribble in neuroblasts. In addition, we show that the LRR domain is sufficient to target Miranda protein to the neuroblast cortex, but that LRR+PDZ will exclude Miranda from the cortex. Our results highlight the importance of both LRR and PDZ domains for the proper localization and function of Scribble in neuroblasts.