Consequences of individual N-glycan deletions and of proteasomal inhibition on secretion of active BACE.

BACE is an aspartic protease involved in the production of a toxic peptide accumulating in the brain of Alzheimer's disease patients. After attainment of the native structure in the endoplasmic reticulum (ER), BACE is released into the secretory pathway. To better understand the mechanisms regulating protein biogenesis in the mammalian ER, we determined the fate of five variants of soluble BACE with 4, 3, 2, 1, or 0 N-linked glycans.

From clinical activities to didactics and research in occupational medicine.

Background: The daily practice of Occupational Physicians in the mot industrialized countries suggests that the frequency of traditional occupational diseases is progressively lowering, their gravity is decreasing, and the etiological factors are changing. This trend should be quantitatively and qualitatively verified with ad hoc studies. The information is particularly relevant for Academic Institutions where medical students and residents in occupational medicine are trained.

Persistent glycoprotein misfolding activates the glucosidase II/UGT1-driven calnexin cycle to delay aggregation and loss of folding competence.

The UDP-glucose:glycoprotein glucosyltransferase (UGT) is a central player of glycoprotein quality control in the endoplasmic reticulum (ER). UGT reglucosylation of nonnative glycopolypeptides prevents their release from the calnexin cycle and secretion. Here, we compared the fate of a glycoprotein with a reversible, temperature-dependent folding defect in cells with and without UGT1.