16 research outputs found
EDEM1 Recognition and Delivery of Misfolded Proteins to the SEL1L-Containing ERAD Complex
BFMP: A Method for Discretizing and Visualizing Pyranose Conformations
We
report a new classification method for pyranose ring conformations
called Best-fit, Four-Membered Plane (BFMP), which describes pyranose
ring conformations based on reference planes defined by four atoms.
The method is able to characterize all asymmetrical and symmetrical
shapes of a pyran ring, is readily automated, easy to interpret, and
maps trivially to IUPAC definitions. It also provides a qualitative
measurement of the distortion of the ring. Example applications include
the analysis of data from crystal structures and molecular dynamics
simulations
The endoplasmic reticulum in pancreatic beta cells of type 2 diabetes patients.
AIMS/HYPOTHESIS: Pancreatic beta cells have highly developed endoplasmic reticulum (ER) due to their role in insulin secretion. Since ER stress has been associated with beta cell dysfunction, we studied several features of beta cell ER in human type 2 diabetes. METHODS: Pancreatic samples and/or isolated islets from non-diabetic controls (ND) and type 2 diabetes patients were evaluated for insulin secretion, apoptosis (electron microscopy and ELISA), morphometric ER assessment (electron microscopy), and expression of ER stress markers in beta cell prepared by laser capture microdissection and in isolated islets. RESULTS: Insulin release was lower and beta cell apoptosis higher in type 2 diabetes than ND islets. ER density volume was significantly increased in type 2 diabetes beta cells. Expression of alpha-mannosidase (also known as mannosidase, alpha, class 1A, member 1) and UDP-glucose glycoprotein glucosyl transferase like 2 (UGCGL2), assessed by microarray and/or real-time reverse transcriptase polymerase chain reaction (RT-PCR), differed between ND and type 2 diabetes beta cells. Expression of immunoglobulin heavy chain binding protein (BiP, also known as heat shock 70 kDa protein 5 [glucose-regulated protein, 78 kDa] [HSPA5]), X-box binding protein 1 (XBP-1, also known as XBP1) and C/EBP homologous protein (CHOP, also known as damage-inducible transcript 3 [DDIT3]) was not higher in type 2 diabetes beta cell or isolated islets cultured at 5.5 mmol/l glucose (microarray and real-time RT-PCR) than in ND samples. When islets were cultured for 24 h at 11.1 mmol/l glucose, there was induction of BiP and XBP-1 in type 2 diabetes islets but not in ND islets. CONCLUSIONS/INTERPRETATION: Beta cell in type 2 diabetes showed modest signs of ER stress when studied in pancreatic samples or isolated islets maintained at physiological glucose concentration. However, exposure to increased glucose levels induced ER stress markers in type 2 diabetes islet cells, which therefore may be more susceptible to ER stress induced by metabolic perturbations.Comparative StudyJournal ArticleResearch Support, Non-U.S. Gov'tinfo:eu-repo/semantics/publishe
EDEM2 and OS-9 Are Required for ER-Associated Degradation of Non-Glycosylated Sonic Hedgehog
Golgi localization of ERManI defines spatial separation of the mammalian glycoprotein quality control system
Bypass of glycan-dependent glycoprotein delivery to ERAD by up-regulated EDEM1
Extensive trimming of mannose residues targets a misfolded glycoprotein for endoplasmic reticulum–associated degradation (ERAD). Surprisingly, overexpression of EDEM1 or its up-regulation by the unfolded protein response bypasses this requirement. Delivery to OS9 in the ER-derived quality control compartment and ERAD becomes mannose trimming–independent, accelerating glycoprotein disposal