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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Yearbook 2016     Display Documents



ID: 723942.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Yearbook 2016
Accumulation of glucosylceramide in the absence of the beta-glucosidase GBA2 alters cytoskeletal dynamics
Authors:Raju, D.; Schonauer, S.; Hamzeh, H.; Flynn, K. C.; Bradke, F.; Vom Dorp, K.; Dormann, P.; Yildiz, Y.; Trotschel, C.; Poetsch, A.; Breiden, B.; Sandhoff, K.; Korschen, H. G.; Wachten, D.
Date of Publication (YYYY-MM-DD):2015-03
Title of Journal:PLoS Genet
Volume:11
Issue / Number:3
Start Page:e1005063
Audience:Not Specified
Abstract / Description: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.
Free Keywords:Actins/chemistry/*metabolism; Animals; Cell Membrane/metabolism/pathology; Cytoskeleton/*genetics/metabolism/pathology; Fibroblasts/metabolism; Glucosylceramides/chemistry/*genetics/metabolism; Humans; Lipid Metabolism/*genetics; Male; Mice; Mice, Knockout; Microtubules/genetics/metabolism/pathology; Pseudopodia/genetics/metabolism/pathology; Sertoli Cells/metabolism/pathology; beta-Glucosidase/*genetics/metabolism
External Publication Status:published
Document Type:Article
Communicated by:n.n.
Affiliations:MPI für physiologische und klinische Forschung
External Affiliations:Axon Growth and Regeneration, German Center for Neurodegenerative Diseases (DZNE e.V.), Bonn, Germany. Institute of Molecular Physiology and Biotechnology of Plants, University of Bonn, Bonn, Germany. Innere Medizin am Landeskrankenhaus Bregenz, Bregenz, Austria. Biochemie der Pflanzen, Ruhr-Universitat Bochum, Bochum, Germany. Life and Medical Sciences Institute (LIMES) c/o Kekule-Institute of Chemistry and Biochemistry, Bonn, Germany. Department of Molecular Sensory Systems, Center of Advanced European Studies and Research, Bonn, Germany.
Identifiers:ISSN:1553-7404 (Electronic) 1553-7390 (Linking) %R 10.1371/journal.pgen.1005063
URL:http://www.ncbi.nlm.nih.gov/pubmed/25803043
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