Wachten laboratory

Lipid-protein interactions

Project details

Glycosphingolipidsare important constituents of cellular membranes. Glucosylceramide (GlcCer) is the simplest glycosphingolipid and serves as a building block for the synthesis of higher-order glycosphingolipids. Defects in the lysosomal beta-glucosidase 1 (GBA1), which cleaves GlcCer to glucose and ceramide, causes accumulation ofGlcCer in lysosomes and, thereby, the severe lipid-storage disorder Gaucher disease.

The function of GBA2 has been elusive for many years. Knockout-mice lacking the non-lysosomal beta-glucosidase 2 (GBA2) accumulate GlcCer outside the lysosomes. The main phenotype of GBA2 knockout-mice is male infertility due to a defect during sperm development.

We aim to nvestigate the molecular mechanism how glucosylceramide controls signaling pathways not only during sperm development, but also in other cell types and subcellular compartments.

Project-related publications

Sphingolipids controlling ciliary and microvillar function

Kaiser F, Huebecker M, Wachten D.

FEBS Lett. 2020 Nov;594(22):3652-3667. doi: 10.1002/1873-3468.13816. Epub 2020 May 29.

Species-specific differences in nonlysosomal glucosylceramidase GBA2 function underlie locomotor dysfunction arising from loss-of-function mutations

Woeste MA, Stern S, Raju DN, Grahn E, Dittmann D, Gutbrod K, Dörmann P, Hansen JN, Schonauer S, Marx CE, Hamzeh H, Körschen HG, Aerts JMFG, Bönigk W, Endepols H, Sandhoff R, Geyer M, Berger TK, Bradke F, Wachten D.

J Biol Chem. 2019 Mar 15;294(11):3853-3871. doi: 10.1074/jbc.RA118.006311. Epub 2019 Jan 20.

The Enigmatic Role of GBA2 in Controlling Locomotor Function

Woeste MA, Wachten D.

Front Mol Neurosci. 2017 Nov 28;10:386. doi: 10.3389/fnmol.2017.00386. eCollection 2017.

Identification of a feedback loop involving β-glucosidase 2 and its product sphingosine sheds light on the molecular mechanisms in Gaucher disease

Schonauer S, Körschen HG, Penno A, Rennhack A, Breiden B, Sandhoff K, Gutbrod K, Dörmann P, Raju DN, Haberkant P, Gerl MJ, Brügger B, Zigdon H, Vardi A, Futerman AH, Thiele C, Wachten D.

J Biol Chem. 2017 Apr 14;292(15):6177-6189. doi: 10.1074/jbc.M116.762831. Epub 2017 Mar 3.

Diastereomer-specific quantification of bioactive hexosylceramides from bacteria and mammals

von Gerichten J, Schlosser K, Lamprecht D, Morace I, Eckhardt M, Wachten D, Jennemann R, Gröne HJ, Mack M, Sandhoff R.

J Lipid Res. 2017 Jun;58(6):1247-1258. doi: 10.1194/jlr.D076190. Epub 2017 Apr 3.

Accumulation of glucosylceramide in the absence of the beta-glucosidase GBA2 alters cytoskeletal dynamics

Raju D, Schonauer S, Hamzeh H, Flynn KC, Bradke F, Vom Dorp K, Dörmann P, Yildiz Y, Trötschel C, Poetsch A, Breiden B, Sandhoff K, Körschen HG, Wachten D.

PLoS Genet. 2015 Mar 24;11(3):e1005063. doi: 10.1371/journal.pgen.1005063. eCollection 2015 Mar.

1-O-acylceramides are natural components of human and mouse epidermis

Rabionet M, Bayerle A, Marsching C, Jennemann R, Gröne HJ, Yildiz Y, Wachten D, Shaw W, Shayman JA, Sandhoff R.

J Lipid Res. 2013 Dec;54(12):3312-21. doi: 10.1194/jlr.M040097. Epub 2013 Sep 27.

The non-lysosomal β-glucosidase GBA2 is a non-integral membrane-associated protein at the endoplasmic reticulum (ER) and Golgi

Körschen HG, Yildiz Y, Raju DN, Schonauer S, Bönigk W, Jansen V, Kremmer E, Kaupp UB, Wachten D.

J Biol Chem. 2013 Feb 1;288(5):3381-93. doi: 10.1074/jbc.M112.414714. Epub 2012 Dec 17.

Project-related funding


Deutsche Forschungsgemeinschaft (DFG)

Project-related scientists

Dagmar Wachten Lab
Dagmar Wachten Lab
Dagmar Wachten Lab

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