Lipid sorting and formation of distinct plasma membrane domains during cell polarization in Drosophila

果蝇细胞极化过程中的脂质分选和不同质膜域的形成

• 批准号: 5396820
• 负责人: Professor Dr. Salim Seyfried
• 金额: --
• 依托单位: Arbeitsgruppe Zoophysiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2003
• 资助国家: 德国
• 起止时间: 2002-12-31 至 2003-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5396820?language=en
• 关键词: Lipid; sorting; formation; distinct; plasma

The sorting of plasma membrane components including proteins and lipids in the trans-Golgi network (TGN) into apical and basolateral transport vesicles and the correct delivery to surface domains are mechanisms by which cell polarity is maintained (1). However, they fail to explain how cell polarity is initially established and which role sorting mechanisms for proteins and lipids may play in this process. In addition, it is not understood whether distinct membrane compartments are established prior to or after formation of a membrane fence that blocks lateral lipid diffusion and what role such a fence may have for targeting mechanisms. Previous studies suggest a role of the endocytic pathway in polarized targeting of protein and lipid components (2,3,4). We want to test whether membrane trafficking along the endocytic and biosynthetic pathway monitored by fluorescent lipid analogs has pronounced effects on the establishment of cell polarity. We propose to test the effects on establishment and maintenance of cellular polarity by studying intracellular lipid transport and by gene inactivation of components of the endocytic pathway in Drosophila. Conversely, some genes for which a role in establishment of cell polarity has been ascribed may function in protein or lipid sorting as well. We will investigate this possibility by employing Drosophila mutants with defects in cellular polarity to characterize whether the existing targeting mechanisms may be affected. Finally, we will use the Drosophila genomic sequence and gene prediction programs to identify candidate transmembrane proteins with a possible role in establishing the membrane fence that separates apical from basolateral membrane compartments. The function of those candidate genes will be tested using existing mutants or RNA interference.

质膜组分（包括跨高尔基体网络（TGN）中的蛋白质和脂质）分选到顶端和基底侧运输囊泡中以及正确递送到表面结构域是维持细胞极性的机制（1）。然而，他们未能解释细胞极性最初是如何建立的，以及蛋白质和脂质的分选机制在这一过程中可能发挥的作用。此外，还不清楚不同的膜隔室是在形成阻断侧向脂质扩散的膜栅栏之前还是之后建立的，以及这种栅栏对于靶向机制可能具有什么作用。先前的研究表明内吞途径在蛋白质和脂质组分的极化靶向中的作用（2，3，4）。我们想测试是否膜运输沿着内吞和生物合成途径监测荧光脂质类似物对细胞极性的建立有显着的影响。我们建议通过研究细胞内脂质转运和果蝇内吞途径组分的基因失活来测试对细胞极性建立和维持的影响。相反，一些基因的作用，在建立细胞极性已被归因于蛋白质或脂质分选以及功能。我们将调查这种可能性，采用果蝇突变体与缺陷的细胞极性，以表征现有的靶向机制是否可能受到影响。最后，我们将使用果蝇的基因组序列和基因预测程序，以确定候选跨膜蛋白与可能的作用，在建立膜栅栏，从基底外侧膜室分开顶端。这些候选基因的功能将使用现有的突变体或RNA干扰进行测试。