Journal Article

DZNE-2020-04187

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Accumulation of glucosylceramide in the absence of the beta-glucosidase GBA2 alters cytoskeletal dynamics.

Raju, D. ; Schonauer, S. ; Hamzeh, H. ; Flynn, K. C.DZNE* ; Bradke, F.DZNE* ; Vom Dorp, K. ; Dörmann, P. ; Yildiz, Y. ; Trötschel, C. ; Poetsch, A. ; Breiden, B. ; Sandhoff, K. ; Körschen, H. G. ; Wachten, D. (Corresponding author)

2015
Public Library of Science San Francisco, Calif.

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Please use a persistent id in citations: doi:10.1371/journal.pgen.1005063

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.

Keyword(s): Actins: chemistry (MeSH) ; Actins: metabolism (MeSH) ; Animals (MeSH) ; Cell Membrane: metabolism (MeSH) ; Cell Membrane: pathology (MeSH) ; Cytoskeleton: genetics (MeSH) ; Cytoskeleton: metabolism (MeSH) ; Cytoskeleton: pathology (MeSH) ; Fibroblasts: metabolism (MeSH) ; Glucosylceramides: chemistry (MeSH) ; Glucosylceramides: genetics (MeSH) ; Glucosylceramides: metabolism (MeSH) ; Humans (MeSH) ; Lipid Metabolism: genetics (MeSH) ; Male (MeSH) ; Mice (MeSH) ; Mice, Knockout (MeSH) ; Microtubules: genetics (MeSH) ; Microtubules: metabolism (MeSH) ; Microtubules: pathology (MeSH) ; Pseudopodia: genetics (MeSH) ; Pseudopodia: metabolism (MeSH) ; Pseudopodia: pathology (MeSH) ; Sertoli Cells: metabolism (MeSH) ; Sertoli Cells: pathology (MeSH) ; beta-Glucosidase: genetics (MeSH) ; beta-Glucosidase: metabolism (MeSH) ; Actins ; Glucosylceramides ; beta-Glucosidase ; beta-glucosidase 2, mouse

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Contributing Institute(s):

1. Axon Growth and Regeneration (AG Bradke)

Research Program(s):

1. 341 - Molecular Signaling (POF3-341) (POF3-341)

Appears in the scientific report 2015

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