A5046195903- Cellular transport and secretion
- Genetic and phenotypic traits in livestock
- Advanced Proteomics Techniques and Applications
- Glycosylation and Glycoproteins Research
- Ubiquitin and proteasome pathways
- Cell Adhesion Molecules Research
- Milk Quality and Mastitis in Dairy Cows
- Monoclonal and Polyclonal Antibodies Research
- RNA Research and Splicing
- Microtubule and mitosis dynamics
- RNA and protein synthesis mechanisms
- Endoplasmic Reticulum Stress and Disease
- Immune Response and Inflammation
- S100 Proteins and Annexins
- Molecular Biology Techniques and Applications
- Signaling Pathways in Disease
- DNA Repair Mechanisms
- Nerve injury and regeneration
- Heat shock proteins research
- Lipoproteins and Cardiovascular Health
- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Galectins and Cancer Biology
- Genomics and Chromatin Dynamics
- Cytokine Signaling Pathways and Interactions
Aarhus University
2013-2025
Lundbeck Foundation
2010-2019
Institute of Biochemistry
1996-2004
University of Bath
1998
Radboud University Medical Center
1997
Radboud University Nijmegen
1997
Aarhus University Hospital
1996
Orano (United States)
1995
Amgen (United States)
1995
Ghent University Hospital
1993
sorLA is a sorting receptor for amyloid precursor protein (APP) genetically linked to Alzheimer's disease (AD). Retromer, an adaptor complex in the endosome-to-Golgi retrieval pathway, has been implicated APP transport because retromer deficiency leads aberrant and processing levels of proteins are altered AD. Here we report that functionally interact neurons control trafficking amyloidogenic APP. We have identified sequence (FANSHY) cytoplasmic domain recognized by VPS26 subunit complex....
The 39-40-kDa receptor-associated protein (RAP) binds to the members of low density lipoprotein receptor gene family and functions as a specialized endoplasmic reticulum/Golgi chaperone. Using RAP affinity chromatography, we have purified novel ∼250-kDa brain isolated corresponding cDNA. gene, designated SORL1, maps chromosome 11q 23/24 encodes 2214-residue type 1 containing furin cleavage site immediately preceding N terminus determined in protein. receptor, sorLA-1, has short cytoplasmic...
Knowledge about carbohydrate recognition domains of galectins, formerly known as S-type animal lectins, is important in understanding their role(s) cell-cell interactions. Here we report the crystal structure human galectin-7 (hGal-7), free form and presence galactose, galactosamine, lactose, N-acetyl-lactosamine at high resolution. This first a galectin determined both carbohydrate-bound forms. The shows fold similar to that prototype galectins -1 -2, but has greater similarity related...
Aggregation of the nerve cell protein alpha-synuclein is a characteristic common neurodegenerative alpha-synucleinopathies like Parkinson's disease and Lewy body dementia, it plays direct pathogenic role as demonstrated by early onset diseases caused mis-sense mutations multiplication gene. We investigated existence pro-aggregatory brain proteins whose dysregulation may contribute to progression, we identified brain-specific p25alpha candidate that preferentially binds in its aggregated...
SorLA/LR11 (250 kDa) is the largest and most composite member of Vps10p-domain receptors, a family type 1 proteins preferentially expressed in neuronal tissue. SorLA binds several ligands, including neurotensin, platelet-derived growth factor-bb, lipoprotein lipase, via complex-formation with amyloid precursor protein it downregulates generation Alzheimer's disease-associated Aβ-peptide. The receptor mainly located vesicles, suggesting function sorting transport. Here we examined SorLA's...
PCNA autoantibodies specific for cyclin/PCNA were used to determine the nuclear distribution of this protein in transformed human amnion cells (AMA) irradiated with ultraviolet light (254 nm) under conditions that induced nucleotide excision DNA repair synthesis. The results showed a striking increase antigen staining non S‐phase was not abolished by cycloheximide (20 μg/ml, added 2 h before irradiation), and is most likely due redistribution pre‐existing cyclin. These observations raise...
Circulating PCSK9 destines low-density lipoprotein receptor for degradation in lysosomes, resulting increased LDL cholesterol. Accordingly, it is an attractive drug target hypercholesterolemia, and results from clinical trials are promising. While the physiological role of cholesterol metabolism well described, its complex mechanism action remains poorly understood, although known to depend on intracellular trafficking. We here identify sortilin, encoded by hypercholesterolemia-risk gene...
Abstract Coronary artery disease is the main cause of death worldwide and accelerated by increased plasma levels cholesterol-rich low-density lipoprotein particles (LDL). Circulating PCSK9 contributes to coronary inducing lysosomal degradation LDL receptor (LDLR) in liver thereby reducing clearance. Here, we show that heparan sulfate proteoglycans are receptors essential for PCSK9-induced LDLR degradation. The sulfate-binding site located prodomain formed surface-exposed basic residues...
We previously isolated and sequenced the ∼250-kDa type 1 receptor sorLA/LR11, a mosaic protein with elements characterizing Vps10p domain family as well low density lipoprotein family. The N terminus of comprises consensus sequence for cleavage by furin (50RRKR53) that precedes truncation found in sorLA from human brain. Here we show sorLA, like sortilin-1/neurotensin receptor-3, whose lumenal consists only, is synthesized proreceptor cleaved late Golgi compartments. conditions propeptide...
A transformation-sensitive human protein (IEF SSP 3521) that is 2-fold up-regulated in SV40-transformed MRC-5 fibroblasts has been purified by two-dimensional gel electrophoresis, microsequenced, and cDNA cloned using oligodeoxyribonucleotides. The 2.1-kilobase encodes a 543-amino acid with calculated molecular mass of 62.6 kDa pI 6.77. Expression the AMA cells vaccinia virus expression system followed electrophoresis showed comigrated IEF 3521. contains tetratricopeptide repeat found...
Abstract A total of 3430 polypeptides (2592 cellular; 838 secreted) from transformed human amnion cells (AMA) labeled with [ 35 S]methionine were separated and recorded using computer‐aided two‐dimensional (2‐D) gel electrophoresis. master 2‐D database cellular protein information that includes both qualitative quantitative annotations has been established. The numbers in this differ those reported an earlier version (Celis et al. Leukemia 1988,2, 561–602) as a result changes the scanning...
To report a single biomarker, psoriasin (Mr 11.0 kd, pI 6.2), calcium binding protein which is expressed largely by stratified squamous epithelia and externalized to the urine of bladder cell carcinoma (SCC) bearing patients.Protein expression profiles SCCs obtained immediately after surgery were analyzed two-dimensional gel electrophoresis Coomassie blue staining. Protein identity was determined microsequencing immunoblotting. in cryosections studied immunofluorescence.Four patients with...
The galectins are a family of β-galactoside-binding proteins implicated in modulating cell-cell and cell-matrix interactions. Here we report the cloning expression novel member this (galectin-7) that correspond to IEF (isoelectric focusing) 17 (12,700 Da; pI, 7.6) human keratinocyte protein data base, is strikingly down-regulated SV40 transformed keratinocytes (K14). cDNA was cloned from λgt11 library using degenerated oligodeoxyribonucleotides back-translated an peptide sequence. encoded by...
Abstract The master two‐dimensional gel database of human keratinocytes currently lists 2980 cellular proteins (2098 isoelectric focusing, IEF; and 882 nonequilibrium pH gradient electrophoresis, NEPHGE) many which correspond to posttranslational modifications. About 20% all recorded have been identified (protein name, organelle components, etc.) they are listed in alphabetical order together with their M r , p I localization credit the investigator(s) that aided identification. Also, we 145...
The sequence of cyclin (proliferating cell nuclear antigen, PCNA), antigen staining throughout the cycle African green monkey kidney cells (BS‐C‐1) has been determined by indirect immunofluorescence using PCNA autoantibodies specific for this protein. Patterns observed between beginning S‐phase and maximum DNA synthesis are similar to those reported in human AMA [(1985) Proc. Natl. Acad. Sci. USA 82, 3262‐3266], while detected thereafter significantly different; most striking feature being...
The development and progression of Alzheimer's disease is linked to excessive production toxic amyloid-β peptide, initiated by β-secretase cleavage the amyloid precursor protein (APP). In contrast, soluble APPα (sAPPα) generated α-secretase known stimulate dendritic branching enhance synaptic function. Regulation APP processing, shift from neurotrophic neurotoxic metabolism remains poorly understood, but cellular localization its interaction with various receptors considered important. We...