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

蛋白糖基化在发育和不同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。甘露甘露糖是由甘露甘露糖1-3和甘露甘露糖0-1 n -乙酰氨基葡萄糖2组成的甘露甘露糖类n -聚糖，传统上被认为是一种植物和无脊椎动物的聚糖。然而，最近的一些出版物表明，在不同的生理和病理生理条件下，脊椎动物细胞中表达了paucimannose。我们在出生后早期的神经干细胞和两种不同的肿瘤细胞系中特异性地检测到paucimannose。肿瘤细胞中paucimannose的表达依赖于细胞的增殖和分化。与特异性识别paucimannose的mannitou抗体孵育细胞（出生后神经干细胞和肿瘤细胞）可显著降低细胞增殖。此外，在病原体感染的人中性粒细胞中发现了paucimansidic蛋白，表明其可能在炎症过程中起作用。由于paucimannose在脊椎动物中的存在是最近才被证实的，并且对其在脊椎动物中的功能几乎一无所知，我们的目标是更详细地分析paucimannose在特定干细胞群体和肿瘤细胞中的表达和功能机制。在阿尔茨海默病患者发生的神经炎症过程中，也将分析少蛋白糖的表达和作用。此外，还将鉴定携带paucimannose的蛋白。最后，将分析paucimannose在体外和体内不同细胞类型（生理和病理生理条件）下的功能。这个项目的结果可能代表了一种理解干细胞发育、肿瘤进展和神经炎症的新方法。

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.