Journal Article

ER retention and degradation as the molecular basis underlying Gaucher disease heterogeneity

Idit Ron and Mia Horowitz

in Human Molecular Genetics

Volume 14, issue 16, pages 2387-2398
Published in print August 2005 | ISSN: 0964-6906
Published online July 2005 | e-ISSN: 1460-2083 | DOI:
ER retention and degradation as the molecular basis underlying Gaucher disease heterogeneity

Show Summary Details


Gaucher disease (GD), an autosomal recessive disease, is characterized by accumulation of glucosylceramide mainly in cells of the reticuloendothelial system, due to mutations in the acid β-glucocerebrosidase gene. Some of the patients suffer from neurological symptoms (type 2 and type 3 patients), whereas patients with type 1 GD do not present neurological signs. The disease is heterogeneous even among patients with the same genotype, implicating that a mutation in the glucocerebrosidase gene is required to cause GD but other factors play an important role in the manifestation of the disease. Glucocerebrosidase is a lysosomal enzyme, synthesized on endoplasmic reticulum (ER)-bound polyribosomes and translocated into the ER. Following N-linked glycosylations, it is transported to the Golgi apparatus, from where it is trafficked to the lysosomes. In this study, we tested glucocerebrosidase protein levels, N-glycans processing and intracellular localization in skin fibroblasts derived from patients with GD. Our results strongly suggest that mutant glucocerebrosidase variants present variable levels of ER retention and undergo ER-associated degradation in the proteasomes. The degree of ER retention and proteasomal degradation is one of the factors that determine GD severity.

Journal Article.  8029 words.  Illustrated.

Subjects: Genetics and Genomics

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.