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Accumulation of Glucosylceramide in the Absence of the Beta-Glucosidase GBA2 Alters Cytoskeletal Dynamics

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Raju,  Diana Nancy
Max Planck Research Group Molecular Physiology, Center of Advanced European Studies and Research (caesar), Max Planck Society;

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Schonauer,  Sophie
Max Planck Research Group Molecular Physiology, Center of Advanced European Studies and Research (caesar), Max Planck Society;

Hamzeh,  Hussein
Max Planck Research Group Molecular Physiology, Center of Advanced European Studies and Research (caesar), Max Planck Society;

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Körschen,  Heinz Gerd
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Max Planck Society;

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Wachten,  Dagmar
Max Planck Research Group Molecular Physiology, Center of Advanced European Studies and Research (caesar), Max Planck Society;

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Citation

Raju, D. N., Schonauer, S., Hamzeh, H., Flynn, K. C., Bradke, F., vom Dorp, K., et al. (2015). Accumulation of Glucosylceramide in the Absence of the Beta-Glucosidase GBA2 Alters Cytoskeletal Dynamics. PLoS Genetics, 11(3): e1005063. doi:10.1371/journal.pgen.1005063.


Cite as: https://hdl.handle.net/11858/00-001M-0000-0028-6191-2
Abstract
Glycosphingolipids are key elements of cellular membranes, thereby, controlling a variety of cellular functions. Accumulation of the simple glycosphingolipid glucosylceramide results in life-threatening lipid storage-diseases or in male infertility. How glucosylceramide regulates cellular processes is ill defined. Here, we reveal that glucosylceramide accumulation in GBA2 knockout-mice alters cytoskeletal dynamics due to a more ordered lipid organization in the plasma membrane. In dermal fibroblasts, accumulation of glucosylceramide augments actin polymerization and promotes microtubules persistence, resulting in a higher number of filopodia and lamellipodia and longer microtubules. Similar cytoskeletal defects were observed in male germ and Sertoli cells from GBA2 knockout-mice. In particular, the organization of F-actin structures in the ectoplasmic specialization and microtubules in the sperm manchette is affected. Thus, glucosylceramide regulates cytoskeletal dynamics, providing mechanistic insights into how glucosylceramide controls signaling pathways not only during sperm development, but also in other cell types.