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New insights into ER and Golgi N-linked glycosylation - Contribution of CDG patients.

Congenital Disorders of Glycosylation (CDG) are a rapidly growing and heterogeneous group of rare, genetic diseases of metabolism. They are severe diseases that are caused by a defective glycosylation of proteins. However, the mechanisms of the fine-tuning of the glycosylation machinery remain poorly understood. Recent evidence, obtained from observations in specific patients, suggested that an adequate maintenance of the Golgi environment in the cells is essential to ensure correct glycosylation. Indeed, we know that the Golgi apparatus has a central role in the trafficking and processing of glycoproteins. With this research project, we have the unique opportunity to investigate the molecular mechanisms by which Golgi homeostasis is maintained, and identify how the altered homeostasis can impact on Golgi function and lead to disease. We will take advantage of the availability of cells from patients with the recently identified MAN1B1 deficiency to investigate the mechanisms of Golgi-mediated stress response. In parallel, we will study the effects of another protein, TMEM165, on the function of the Golgi. For the second part, we plan to use a mouse model to study the links between the genetic defects in Golgi glycosylation and the skeletal abnormalities that are observed in TMEM165-CDG patients, and that probably also result from a disturbed function of the Golgi. The latter will contribute to our understanding of bone and cartilage development.

Date:1 Oct 2012 →  30 Sep 2018
Keywords:CDG patients, Glycosylation, Golgi N-linked, ER
Disciplines:Genetics, Systems biology, Molecular and cell biology