Massimi Paola, Narayan Nisha, Thomas Miranda, Gammoh Noor, Strand Susanne, Strand Dennis, Banks Lawrence
International Centre for Genetic Engineering and Biotechnology, Padriciano 99, I-34012 Trieste, Italy.
Exp Cell Res. 2008 Nov 1;314(18):3306-17. doi: 10.1016/j.yexcr.2008.08.016. Epub 2008 Sep 3.
The proper function of the Scribble tumour suppressor complex is dependent upon the correct localisation of its components. Previously we observed dynamic relocalisation of the hDlg component under conditions of osmotic stress. We now show that the other two components of the complex, hScrib and Hugl-1 display similar patterns of expression. We demonstrate, by shRNA ablation of hScrib expression, that hDlg and Hugl-1 are in part dependent upon hScrib for their correct localization. However under conditions of osmotic stress this apparent dependency no longer exists: hDlg and Hugl-1 localise to cell membranes independently of hScrib. We also demonstrate an interaction between the three components of the hScrib complex and the tSNARE syntaxin 4, and show that correct localization of the Scrib complex is in part tSNARE dependent. This is the first detailed analysis of the co-localisation and function of the hScrib complex in mammalian cells and demonstrates a direct link between the control of the hScrib complex and vesicle transport pathways.
Scribble肿瘤抑制复合物的正常功能取决于其组分的正确定位。此前我们观察到在渗透压应激条件下hDlg组分的动态重新定位。我们现在表明该复合物的其他两个组分hScrib和Hugl-1表现出相似的表达模式。我们通过shRNA敲除hScrib的表达证明，hDlg和Hugl-1的正确定位部分依赖于hScrib。然而在渗透压应激条件下，这种明显的依赖性不再存在：hDlg和Hugl-1独立于hScrib定位于细胞膜。我们还证明了hScrib复合物的三个组分与tSNARE syntaxin 4之间存在相互作用，并表明Scrib复合物的正确定位部分依赖于tSNARE。这是对哺乳动物细胞中hScrib复合物共定位和功能的首次详细分析，并证明了hScrib复合物的控制与囊泡运输途径之间的直接联系。
