Analysis of expression and function of paucimannose - a new type of glycoslyation in vertebrate cells - in neural stem cells, glioblastoma cancer cells and neuroinflammatory processes

少甘露糖（脊椎动物细胞中的一种新型糖基化）在神经干细胞、胶质母细胞瘤癌细胞和神经炎症过程中的表达和功能分析

• 批准号: 291333515
• 负责人: Privatdozentin Dr. Simone Diestel
• 金额: --
• 依托单位: Abteilung Human Metabolomics
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2016
• 资助国家: 德国
• 起止时间: 2015-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/291333515?language=en
• 关键词: Analysis; expression; function; paucimannose; new

Protein glycosylation has received much attention during the last years since it became evident that it plays important regulatory roles during development and different pathophysiological conditions. Paucimannose is a mannosidic N-glycan composed of the monosaccharides mannose1-3fucose0-1N-acetylglucosamine2 that has classically been considered as a plant and invertebrate glycan. However, some recent publications demonstrated paucimannose expression in vertebrate cells in different physiological and pathophysiological conditions.We detected paucimannose specifically in early postnatal neural stem cells and in two different tumor cell lines. Expression of paucimannose in tumor cells was dependent on proliferation and differentiation of cells. Incubation of cells (postnatal neural stem cell and tumor cells) with Mannitou-antibody that specifically recognizes paucimannose resulted in significantly decreased cell proliferation. Furthermore, paucimannosidic proteins were identified in pathogene-infected human neutrophils indicating a possible role in inflammatory processes. Since the existence of paucimannose in vertebrates has only recently been demonstrated and almost nothing is known about its function in vertebrates, we aim to analyse the expression and functional mechanisms of paucimannose in specific stem cell populations and tumor cells with the proposed project in more detail. The expression and role of paucimannose in neuroinflammatory processes as occurring in Alzheimer dementia patients will also be analyzed. Furthermore, paucimannose carrying proteins will be identified. Finally, the function of paucimannose will be analysed in vitro and in vivo in different cell types (physiological and pathophysiological conditions). The results of this project could potentially represent a novel approach to understand stem cell development tumor progression and neuroinflammation.

蛋白质糖基化在发育和不同的病理生理条件下起着重要的调节作用，近年来受到了广泛的关注。少甘露糖是由单糖甘露糖1 - 3岩藻糖0 - 1 N-乙酰葡糖胺2组成的甘露糖苷N-聚糖，其被经典地认为是植物和无脊椎动物聚糖。然而，最近的一些出版物表明，在脊椎动物细胞在不同的生理和病理生理条件下的表达。我们检测到少甘露糖特异性在出生后早期的神经干细胞和两种不同的肿瘤细胞系。肿瘤细胞中少甘露糖的表达依赖于细胞的增殖和分化。用特异性识别少甘露糖的甘露糖抗体孵育细胞（出生后神经干细胞和肿瘤细胞）导致细胞增殖显著降低。此外，在病原体感染的人嗜中性粒细胞中鉴定了少甘露糖苷蛋白，表明其在炎症过程中可能起作用。由于少甘露糖在脊椎动物中的存在只是最近才被证明，并且几乎对其在脊椎动物中的功能一无所知，因此我们的目标是更详细地分析少甘露糖在特定干细胞群体和肿瘤细胞中的表达和功能机制。还将分析少甘露糖在阿尔茨海默痴呆患者中发生的神经炎症过程中的表达和作用。此外，将鉴定携带少甘露糖的蛋白质。最后，将在体外和体内不同细胞类型（生理和病理生理条件）中分析少甘露糖的功能。该项目的结果可能代表一种新的方法来了解干细胞发育、肿瘤进展和神经炎症。