title: Accumulation of glucosylceramide in the absence of the beta-glucosidase GBA2 alters cytoskeletal dynamics.
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.
authors: Minerva Research Group-Molecular Physiology, Center of Advanced European Studies and Research, Bonn, Germany.
authors: Diana
authors: D
authors: Raju
authors: Minerva Research Group-Molecular Physiology, Center of Advanced European Studies and Research, Bonn, Germany.
authors: Sophie
authors: S
authors: Schonauer
authors: Minerva Research Group-Molecular Physiology, Center of Advanced European Studies and Research, Bonn, Germany.
authors: Hussein
authors: H
authors: Hamzeh
authors: Axon Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE e.V.), Bonn, Germany.
authors: Kevin C
authors: KC
authors: Flynn
authors: Axon Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE e.V.), Bonn, Germany.
authors: Frank
authors: F
authors: Bradke
authors: Institute of Molecular Physiology and Biotechnology of Plants, University of Bonn, Bonn, Germany.
authors: Katharina
authors: K
authors: Vom Dorp
authors: Institute of Molecular Physiology and Biotechnology of Plants, University of Bonn, Bonn, Germany.
authors: Peter
authors: P
authors: Dörmann
authors: Innere Medizin am Landeskrankenhaus Bregenz, Bregenz, Austria.
authors: Yildiz
authors: Y
authors: Yildiz
authors: Biochemie der Pflanzen, Ruhr-Universität Bochum, Bochum, Germany.
authors: Christian
authors: C
authors: Trötschel
authors: Biochemie der Pflanzen, Ruhr-Universität Bochum, Bochum, Germany.
authors: Ansgar
authors: A
authors: Poetsch
authors: Life and Medical Sciences Institute (LIMES) c/o Kekulé-Institute of Chemistry and Biochemistry, Bonn, Germany.
authors: Bernadette
authors: B
authors: Breiden
authors: Life and Medical Sciences Institute (LIMES) c/o Kekulé-Institute of Chemistry and Biochemistry, Bonn, Germany.
authors: Konrad
authors: K
authors: Sandhoff
authors: Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany.
authors: Heinz G
authors: HG
authors: Körschen
authors: Minerva Research Group-Molecular Physiology, Center of Advanced European Studies and Research, Bonn, Germany.
authors: Dagmar
authors: D
authors: Wachten
mesh_terms: D000199:Actins / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D003599:Cytoskeleton / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism; D005963:Glucosylceramides / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008870:Microtubules / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D011554:Pseudopodia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012708:Sertoli Cells / Q000378:metabolism / Q000473:pathology; D001617:beta-Glucosidase / Q000235:genetics* / Q000378:metabolism
chemical_list: D000199:Actins; D005963:Glucosylceramides; D001617:beta-Glucosidase; C517538:beta-glucosidase 2, mouse