- Autophagy in Disease and Therapy
- Endoplasmic Reticulum Stress and Disease
- Cell Adhesion Molecules Research
- Cannabis and Cannabinoid Research
- Alzheimer's disease research and treatments
- Lipid metabolism and biosynthesis
- Protease and Inhibitor Mechanisms
- Adenosine and Purinergic Signaling
- Monoclonal and Polyclonal Antibodies Research
- Cellular transport and secretion
- Mitochondrial Function and Pathology
- Calcium signaling and nucleotide metabolism
- Immune Response and Inflammation
- Genetics, Aging, and Longevity in Model Organisms
- NF-κB Signaling Pathways
- Cerebral Venous Sinus Thrombosis
- Lysosomal Storage Disorders Research
- Machine Learning in Bioinformatics
- Platelet Disorders and Treatments
- Cellular Mechanics and Interactions
- S100 Proteins and Annexins
- Immunotherapy and Immune Responses
- Toxoplasma gondii Research Studies
- Heat shock proteins research
- Wnt/β-catenin signaling in development and cancer
Johannes Gutenberg University Mainz
2015-2024
University Medical Center of the Johannes Gutenberg University Mainz
2015-2024
Inserm
2023
Université de Strasbourg
2023
Justus-Liebig-Universität Gießen
1999-2009
Synthasome (United States)
2009
Advanced Tissue (United States)
2001-2002
Columbia University
1993-1998
Sheba Medical Center
1994
Max Planck Society
1993
The aim of this investigation was to identify the domains type IV collagen participating in cell binding and surface receptor involved. A major site found trimeric cyanogen bromide-derived fragment CB3, located 100 nm away from NH2 terminus molecule, which triple-helical conformation is stabilized by interchain disulfide bridges. Cell attachment assays with CB3 revealed comparable activities. Antibodies against inhibited on completely 80%. ability bind cells strictly dependent. Four trypsin...
The triple-helical cyanogen-bromide-derived fragment CB3[IV] of collagen IV, located 100 nm from the N-terminus molecule, contains binding sites for integrins alpha 1 beta and 2 1. To investigate interaction these we performed solid-phase inhibition assays using as receptor isolated ligands used were binding-site-bearing trimeric peptide its shorter tryptic fragments F1-F4. Using titration curves, in which soluble receptors to coated analyzed, different but adjacent areas CB3[IV]....
We report here the analysis of potential ligand binding domains within human integrin a1 subunit, a known collagedaminin receptor.This is effectively blocked by mouse monoclonal antibody 1B3.1.A truncated version subunit lacking NH,terminal half extracellular domain not recognized 1B3.1.Furthermore, we have isolated cDNA containing I from chicken bearing significant homology to and rat sequences.Replacing with its counterpart led surface expression functional heterodimer endogenous p, on NIH...
Macroautophagy is a degradative pathway that sequesters and transports cytosolic cargo in autophagosomes to lysosomes, its deterioration affects intracellular proteostasis. Membrane dynamics accompanying autophagy are mostly elusive depend on trafficking processes. RAB GTPase activating proteins (RABGAPs) important factors for the coordination of cellular vesicle transport systems, several TBC (TRE2-BUB2-CDC16) domain-containing RABGAPs associated with autophagy. Employing C. elegans human...
Dysfunction of autophagy and disturbed protein homeostasis are linked to the pathogenesis human neurodegenerative diseases modulation as clearance process has become one key pharmacological target. Due role sigma-1 receptors (Sig-1R) in learning memory, described pleiotropic neuroprotective effects various experimental paradigms, Sig-1R activation is recognized potential approach for prevention therapy neurodegeneration and, interestingly, amyotrophic lateral sclerosis associated with...
Transcranial color-coded duplex sonography (TCCS) of intracranial veins and sinuses in adults is a new, emerging application ultrasonographic imaging. This study reports standardized examination protocol for venous TCCS provides reference data clinical application.In 130 healthy volunteers (mean age, 45.9+/-16.9 years; range, 14 to 77 years) the system was examined using frequency-based transtemporal TCCS. Identification rate, blood flow velocity, resistance index, systolic/diastolic ratio...
Many integrin receptors localize to focal contact sites upon binding their ligand. However, unoccupied do not sites. Because the beta 1 cytoplasmic domain appears have a localization signal, there must be mechanism by which this is kept inactive in state and becomes exposed or activated occupied receptor. We considered that involves alpha subunit domain. To test hypothesis, we established two NIH 3T3 cell lines express either human wild-type (HA1 cells) deleted (CYT cells). Both similar...
Numerous scaffolds have been proposed for use in connective tissue engineering. Although these direct cell migration and attachment, many are biologically inert thus lack the physiological stimulus to attract cells induce mitogenesis matrix synthesis. In current study, a bioactive scaffold was created by combining synthetic with growth factor-rich plasma (GFRP), an autologous concentration of factors derived from platelet-rich preparation. vitro tendon proliferation synthesis on...
Recent studies provide evidence that wild-type Cu/Zn-superoxide dismutase (SOD1(hWT)) might be an important factor in mutant SOD1-mediated amyotrophic lateral sclerosis (ALS). In order to investigate its functional role the pathogenesis of ALS, we designed fusion proteins two SOD1 monomers linked by a polypeptide. We demonstrated wild-type-like mutants, but not SOD1(G85R) homodimers, as well heterodimers including SOD1(G85R)-SOD1(hWT) display activity. Mutant homodimers showed increased...
Macroautophagy is a conserved degradative pathway and its deterioration linked to disturbances in cellular proteostasis multiple diseases. Here, we show that the RAB GTPase RAB18 modulates autophagy primary human fibroblasts. The knockdown of results decreased autophagic activity, while overexpression enhances pathway. Importantly, this function dependent on RAB3GAP1 RAB3GAP2, which might act as GEFs stimulate activity GTPase. Moreover, deteriorates intracellular accumulation ubiquitinated...
Resource10 October 2022Open Access Transparent process Lipid and protein content profiling of isolated native autophagic vesicles Daniel Schmitt The Autophagy Lab, Institute Pathobiochemistry, University Medical Center the Johannes Gutenberg University, Mainz, Germany Contribution: Conceptualization, Data curation, Formal analysis, Validation, Investigation, Writing - review & editing Search for more papers by this author Süleyman Bozkurt orcid.org/0000-0003-4965-3195 Biochemistry II,...
Autophagy is dependent on appropriate lipid supply for autophagosome formation. The regulation of acquisition and the autophagy network response to lipid-limiting conditions are mostly elusive. Here, we show that knockout RAB GTPase RAB18 interferes with droplet catabolism, causing an impaired fatty acid release. resulting reduced lipid-droplet-derived availability influences provokes adaptive modifications network. These adjustments include increased expression phosphorylation ATG2B as well...
Processing of amyloid precursor protein (APP) is a well acknowledged central pathogenic mechanism in Alzheimer disease. However, influences age-associated cellular alterations on the biochemistry APP processing have not been studied molecular detail so far. Here, we report that endogenous down-regulated during aging normal human fibroblasts (IMR-90). The generation intracellular cleavage products C99, C83, and AICD gradually declines with increasing life span accompanied by reduced secretion...
Protein stability under changing conditions is of vital importance for the cell and control a fine-tuned network molecular chaperones. Aging age-related neurodegenerative diseases are directly associated with enhanced protein instability. Employing C. elegans expressing GFP-tagged luciferase as reporter evaluation we show that chaperoning strategy body wall muscle cells neurons significantly different both differently affected by aging. Muscle young worms largely resistant to heat stress,...
Abstract The sirtuin (SIRT) protein family has been of major research interest over the last decades because their involvement in aging, cancer, and cell death. SIRTs have implicated gene metabolic regulation through capacity to remove acyl groups from lysine residues proteins an NAD + -dependent manner, which may alter individual properties as well histone–DNA interaction. Since regulate a wide range different signaling cascades, fine-tuned homeostasis these is imperative guarantee function...
Objective - The intercellular adhesion molecule-1 (ICAM-1) is a member of the Ig supergene family. ICAM-1 expressed on various cells like peripheral blood lymphocytes, endothelial or thymic and cell surface form supposed to be shed into soluble form. expression induced by cytokines Interleukin-1, TNF alpha interferon gamma. aim study was investigate whether changes in cerebrospinal fluid (CSF) are indicative for disease activity patients with multiple sclerosis (MS). Material methods In all...
Abstract The cellular protein homeostasis (proteostasis) network responds effectively to insults. In a functional screen in C. elegans , we recently identified the gene receptor-mediated endocytosis 8 ( rme-8; human ortholog: DNAJC13 ) as component of proteostasis network. Accumulation aggregation-prone proteins, such amyloid-β 42 (Aβ), α-synuclein, or mutant Cu/Zn-superoxide dismutase (SOD1), were aggravated upon knockdown rme-8/DNAJC13 and cell lines, respectively. is involved endosomal...
The membrane proximal regions of integrin alpha and beta subunits are highly conserved in evolution. In particular, all share the KXGFFKR sequence at beginning their cytoplasmic domains. Previous work has shown that this domain is important receptor assembly. Using chimeric subunits, we show native domains both must be present for efficient Most strikingly, 1 with reciprocally swapped intracellular dimerize selectively into collagen IV receptors expressed high levels on surface. However,...
Selective autophagy receptors (SARs) are central to cellular homeostatic and organellar recycling pathways. Over the last two decades, more than 30 SARs have been discovered validated using a variety of experimental approaches ranging from cell biology biochemistry, including high-throughput imaging screening methods. Yet, extent selective pathways operating under various contexts, for example, basal starvation conditions, remains unresolved. Currently, our knowledge all known their...