English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

The non-lysosomal beta-glucosidase GBA2 is a non-integral membrane-associated protein at the ER and Golgi

MPS-Authors
/persons/resource/persons182745

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

/persons/resource/persons182758

Raju,  D. N.
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Max Planck Society;

/persons/resource/persons182765

Schonauer,  S.
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Max Planck Society;

/persons/resource/persons182720

Boenigk,  W.
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Max Planck Society;

/persons/resource/persons182740

Jansen,  V.
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Max Planck Society;

/persons/resource/persons182743

Kaupp,  U. B.
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Max Planck Society;

/persons/resource/persons182737

Wachten,  D.
Department of Molecular Sensory Systems, Center of Advanced European Studies and Research (caesar), Max Planck Society;

Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Körschen, H. G., Yildiz, Y., Raju, D. N., Schonauer, S., Boenigk, W., Jansen, V., et al. (2013). The non-lysosomal beta-glucosidase GBA2 is a non-integral membrane-associated protein at the ER and Golgi. The Journal of Biological Chemistry, 288(5), 3381-3393. doi:10.1074/jbc.M112.414714.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0028-61BF-B
Abstract
GBA1 and GBA2 are both beta-glucosidases, which cleave glucosylceramide (GlcCer) to glucose and ceramide. GlcCer is a main precursor for higher-order glycosphingolipids, but might also serve as intracellular messenger. Mutations in the lysosomal GBA1 underlie Gaucher disease, the most common lysosomal storage disease in humans. Knocking-out the non-lysosomal GBA2 in mice results in accumulation of GlcCer outside the lysosomes in various tissues, e.g. testis and liver, and impairs sperm development and liver regeneration. However, the underlying mechanisms are not well understood. To reveal the physiological function of GBA2 and, thereby, of the non-lysosomal GlcCer pool, it is important to characterise the localisation of GBA2 and its activity in different tissues. Thus, we generated GBA2-specific antibodies and developed an assay that discriminates between GBA1 and GBA2 without the use of detergent. We show that GBA2 is not, as previously thought, an integral membrane protein, but rather a cytosolic protein that tightly associates with cellular membranes. The interaction with the membrane, in particular with phospholipids, is important for its activity. GBA2 is localised at the ER and Golgi, which puts GBA2 in a key position for a lysosomal-independent route of GlcCer-dependent signalling. Furthermore, our results suggest that GBA2 might affect the phenotype of Gaucher disease, because GBA2 activity is reduced in Gba1-knockout fibroblasts and fibroblasts from a Gaucher patient. Our results provide the basis to understand the mechanism for GBA2 function in vivo and might help to unravel the role of GBA2 during pathogenesis of Gaucher disease.