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

• Applicant: Privatdozentin Dr. Simone Diestel
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Cell Biology
• Term: from 2016 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 291333515

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.

• DFG Programme: Research Grants