Role of protein S-acylation in branching of dendrites?

蛋白质 S-酰化在树突分支中的作用？

• 批准号: 283137578
• 负责人: Professor Dr. Felix Wilhelm Theodor Wieland
• 金额: --
• 依托单位: Biochemie-Zentrum (BZH)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2015
• 资助国家: 德国
• 起止时间: 2014-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/283137578?language=en
• 关键词: Role; protein; acylation; branching; dendrites

Whereas palmitoylation of transmembrane proteins has been shown to initiate conformational changes, regulate membrane domain association or protein complex formation, alterations of cell morphology have not been established. We found that the palmitoylated TMD of a viral glycoprotein causes arborisation of the plasma membrane (PM) in cultured cells, and that specific inhibition of this lipidation largely abolishes this branching. Therefore, we hypothesize that palmitoylation of the TMD of specific transmembrane proteins is involved in membrane branching, e.g. dentrite formation. In this application we propose to identify eukaryotic transmembrane protein(s) that arborise membranes, using dentrites as a model. To this end we plan to analyse cell morphology after ectopic expression of a set of bioinformatically identified mammalian palmitoylable candidate proteins in cell culture, complemented by a neuronal cell-specific RNAi-screen in Drosophila. Resulting proteins will be validated by cell biological approaches and characterized biochemically. We intend to gain first insights into the mechanism underlying branching of membranes.

尽管跨膜蛋白的棕榈酰化已被证明可以引发构象变化，调节膜结构域缔合或蛋白质复合物的形成，但细胞形态的改变尚未建立。我们发现，棕榈酰化的TMD的病毒糖蛋白的质膜（PM）在培养的细胞中的树枝状化，并在很大程度上消除这种分支的脂化的特异性抑制。因此，我们假设棕榈酰化的TMD的特定跨膜蛋白参与膜分支，如树枝状突起的形成。在这个应用中，我们提出了确定真核细胞的跨膜蛋白（S），树枝状膜，使用树突作为模型。为此，我们计划分析细胞形态后，异位表达的一组生物信息学鉴定的哺乳动物palmitoylable候选蛋白在细胞培养物中，辅以神经元细胞特异性RNAi屏幕在果蝇。所得蛋白质将通过细胞生物学方法进行验证，并进行生物化学表征。我们打算获得第一次深入了解膜的分支的机制。