Engrailed-2 and inflammation convergently and independently impinge on cerebellar Purkinje cell differentiation.

Autism spectrum disorders (ASD) have a complex pathogenesis thought to include both genetic and extrinsic factors. Among the latter, inflammation of the developing brain has recently gained growing attention. However, how genetic predisposition and inflammation might converge to precipitate autistic behavior remains elusive.

Abrogation of glucosidase I-mediated glycoprotein deglucosylation results in a sick phenotype in fission yeasts: Model for the human MOGS-CDG disorder.

Glucosidase I (GI) removes the outermost glucose from protein-linked GlcManGlcNAc (G3M9) in the endoplasmic reticulum (ER). Individuals with congenital disorders of glycosylation MOGS-CDG bear mutations in the GI-encoding gene (). Although GI absence has been reported to produce lethality in yeasts, here we obtained two viable Δ mutants, one with a very sick but not lethal phenotype (Δ) and the other with a healthier one (Δ).

A novel hepatitis B virus species discovered in capuchin monkeys sheds new light on the evolution of primate hepadnaviruses.

Background & Aims: All known hepatitis B virus (HBV) genotypes occur in humans and hominoid Old World non-human primates (NHPs). The divergent woolly monkey HBV (WMHBV) forms another orthohepadnavirus species. The evolutionary origins of HBV are unclear.

Misfolded endoplasmic reticulum retained subunits cause degradation of wild-type subunits of arylsulfatase A heteromers.

Arylsulfatase A is an oligomeric lysosomal enzyme. In the present study, we use this enzyme as a model protein to examine how heteromerization of wild-type and misfolded endoplasmic reticulum-degraded arylsulfatase A polypeptides affects the quality control of wild-type arylsulfatase A subunits. Using a conformation sensitive monoclonal antibody, we show that, within heteromers of misfolded and wild-type arylsulfatase A, the wild-type subunits are not fully folded.

Human endo-alpha1,2-mannosidase is a Golgi-resident type II membrane protein.

The cDNA for human endo-alpha1,2-mannosidase was reconstructed using two independent EST-clones and its properties characterized. The 2837 bp cDNA construct contained a 1389 bp open reading frame (ORF) encoding for 462 amino acids and an approximately 53.6 kDa protein, respectively.

(Arg)3 within the N-terminal domain of glucosidase I contains ER targeting information but is not required absolutely for ER localization.

Glucosidase I is an endoplasmic reticulum (ER) type II membrane enzyme that cleaves the distal alpha1,2-glucose of the asparagine-linked GlcNAc2-Man9-Glc3 precursor. To identify sequence motifs responsible for ER localization, we prepared a protein chimera by transferring the cytosolic and transmembrane domain of glucosidase I to the luminal domain of Golgi-Man9-mannosidase. The GIM9 hybrid was overexpressed in COS 1 cells as an ER-resident protein that displayed alpha1,2-mannosidase activity, excluding the possibility that the glucosidase I-specific domains interfere with folding of the Man9-mannosidase catalytic domain.

Processing of N-linked carbohydrate chains in a patient with glucosidase I deficiency (CDG type IIb).

Recently, we reported a novel congenital disorder of glycosylation (CDG-IIb) caused by severe deficiency of the glucosidase I. The enzyme cleaves the alpha1,2-glucose residue from the asparagine-linked Glc(3)-Man(9)-GlcNAc(2) precursor, which is crucial for oligosaccharide maturation. The patient suffering from this disease was compound-heterozygous for two mutations in the glucosidase I gene, a T-->C transition in the paternal allele and a G-->C transition in the maternal allele.