A5048267255- Cellular transport and secretion
- Cell Adhesion Molecules Research
- Lipid Membrane Structure and Behavior
- RNA Research and Splicing
- Neuroscience and Neuropharmacology Research
- Nuclear Structure and Function
- Neurogenesis and neuroplasticity mechanisms
- Platelet Disorders and Treatments
- Epigenetics and DNA Methylation
- Mitochondrial Function and Pathology
- Endoplasmic Reticulum Stress and Disease
- Cholinesterase and Neurodegenerative Diseases
- Genetic and Kidney Cyst Diseases
- Pluripotent Stem Cells Research
- Pancreatic function and diabetes
- Pregnancy and preeclampsia studies
- Caveolin-1 and cellular processes
- Biotin and Related Studies
- RNA modifications and cancer
- Retinal Development and Disorders
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Blood Coagulation and Thrombosis Mechanisms
- RNA Interference and Gene Delivery
- Renal and related cancers
- Axon Guidance and Neuronal Signaling
Heidelberg University
2016-2025
Center for Neurosciences
2009-2024
Heidelberg University
2022
Freie Universität Berlin
2007-2008
Springer Nature (Germany)
2008
Max Planck Institute of Molecular Cell Biology and Genetics
1999-2000
Using a new mAb raised against the mouse neuroepithelium, we have identified and cDNA-cloned prominin, an 858-amino acid-containing, 115-kDa glycoprotein. Prominin is novel plasma membrane protein with N-terminal extracellular domain, five transmembrane segments flanking two short cytoplasmic loops large glycosylated domains, C-terminal domain. DNA sequences from Caenorhabditis elegans predict existence of same features, suggesting that prominin conserved between vertebrates invertebrates....
The human AC133 antigen and mouse prominin are structurally related plasma membrane proteins. However, their tissue distribution is distinct, with the being found on hematopoietic stem progenitor cells various epithelial cells. To determine whether orthologues or distinct members of a protein family, we examined cell line Caco-2 for possible expression antigen. By both immunofluorescence immunoprecipitation, was to be expressed surface Interestingly, immunoreactivity antigen, but not its...
The disks of vertebrate photoreceptors are produced by outgrowths the plasma membrane. Hence genes that encode retinal proteins targeted to membrane protrusions represent candidates for inherited degenerations. One such candidate is gene encoding human prominin (mouse)-like 1 (PROML1, previously known as AC133 antigen) which belongs family 5-transmembrane domain proteins. Murine (prom) shows a strong preference in variety epithelial cells whereas PROML1 expressed retinoblastoma cell lines...
Intracellular transport and homeostasis of the endomembrane system in eukaryotic cells depend on formation fusion vesicular carriers. Coat protein complex (COP) II vesicles export newly synthesized secretory proteins from endoplasmic reticulum (ER), whereas COPI facilitate traffic Golgi to ER intra-Golgi transport. Mammalian express various isoforms COPII coat proteins. To investigate roles paralogs, we have combined vitro vesicle reconstitution semi-intact with SILAC-based mass...
Toxic signaling by extrasynaptic NMDA receptors (eNMDARs) is considered an important promoter of amyotrophic lateral sclerosis (ALS) disease progression. To exploit this therapeutically, we take advantage TwinF interface (TI) inhibition, a pharmacological principle that, contrary to classical NMDAR pharmacology, allows selective elimination eNMDAR-mediated toxicity via disruption the NMDAR/TRPM4 death complex while sparing vital physiological functions synaptic NMDARs. Post-disease onset...
Complement effects on human polymorphonuclear leukocytes (PMN) have generally been ascribed to the anaphylatoxin C5a, which induces degranulation, superoxide anion generation, migration, and cell aggregation via interaction with membrane receptors. We here report that complement activation surface of antibody-sensitized PMN provokes generation potent lipid mediator leukotriene B4 (LTB4) in strict dependence component C8, but absence detectable C9. The kinetics LT are rapid, comparable those...
Prominin-1/CD133 is a five-membrane-span glycoprotein that thought to act as an organizer of plasma-membrane protrusions. Here, we report the molecular and cell-biological characterization four novel prominin-1 splice variants isolated from mouse testis cDNA library referred prominin-1.s3 prominin-1.s6. Compared with kidney-derived prominin-1.s1, s3, s4 s5 contain distinct cytoplasmic C-terminal domain. The bear, in addition, two one inframe deletion(s), respectively, extracellular domains....
Synaptic activity initiates many adaptive responses in neurons. Here we report a novel form of structural plasticity dissociated hippocampal cultures and slice preparations. Using recently developed algorithm for three-dimensional image reconstruction quantitative measurements cell organelles, found that nuclei from neurons are highly infolded unequally sized nuclear compartments. Nuclear infoldings dynamic structures, which can radically transform the geometry nucleus response to neuronal...
Abstract Tauopathies such as Alzheimer’s disease are characterized by aggregation and increased phosphorylation of the microtubule-associated protein tau. Tau’s pathological changes closely linked to neurodegeneration, making tau a prime candidate for intervention. We developed an approach monitor aggregation-prone human in living neurons. identified 2-phenyloxazole (PHOX) derivatives putative polypharmacological small molecules that interact with modulate kinases. found PHOX15 inhibits...
Neuroendocrine secretory granules, the storage organelles for neuropeptides and hormones, are formed at trans-Golgi network, stored inside cell exocytosed upon stimulation. Previously, we have reported that newly granules of PC12 cells transported in a microtubule-dependent manner from network to F-actin-rich cortex, where they undergo short directed movements exhibit homogeneous distribution. Here provide morphological biochemical evidence myosin Va is associated with granules. Expression...
Coatomer, the coat protein of complex (COP)I-vesicles, is a soluble made up seven subunits, alpha-, beta-, beta'-, gamma-, delta-, epsilon-, and zeta-COP. Higher eukaryotes have two paralogous versions gamma- zeta- termed gamma1- gamma2-COP zeta1- zeta2-COP. Different combinations these subunits are known to exist within coatomer complexes, gamma1/zeta1-, gamma1/zeta2-, gamma2/zeta1-COP represent major populations in mammals. The role COPI vesicles early secretory pathway subject...
Oxidative stress leads to T-cell hyporesponsiveness or death. The actin-binding protein cofilin is oxidized during oxidative stress, which provokes a stiff actin cytoskeleton and hyporesponsiveness. Here, we show that long-term translocation of into the mitochondria necrotic-like programmed cell death (PCD) in human T cells. Notably, mutants functionally mimic oxidation by single mutation at oxidation-sensitive cysteins (Cys-39 Cys-80) predominately localize within mitochondria. expression...
Focal swellings of dendrites (“dendritic blebbing”) together with structural damage mitochondria and the endoplasmic reticulum (ER) are morphological hallmarks glutamate neurotoxicity, also known as excitotoxicity. These pathological alterations generally thought to be caused by so-called “overactivation” N-methyl-D-aspartate receptors (NMDARs). Here, we demonstrate that activation extrasynaptic NMDARs, specifically when forming a protein–protein complex TRPM4, drives these traits. In...
Prominin is a recently identified polytopic membrane protein expressed in various epithelial cells, where it selectively associated with microvilli. When non-epithelial prominin enriched plasma protrusions. This raises the question of whether selective association microvilli cells solely due to its preference for, and stabilization in, protrusions, or both sorting apical domain subsequent enrichment To investigate this question, we have generated stably transfected MDCK expressing either...
Abstract Prominin‐1 (CD133) is a cholesterol‐interacting pentaspan membrane glycoprotein specifically associated with plasma protrusions. expressed by various stem and progenitor cells, notably neuroepithelial progenitors found in the developing embryonic brain. Here, we further investigated its expression murine Biochemical analyses of brain membranes at early stages development revealed two distinct splice variants prominin‐1, s1 s3, which have different cytoplasmic C‐terminal domains. The...
The high pathogenicity of the Ebola virus reflects multiple concurrent processes on infection. Among other important determinants, fusogenic glycoprotein (GP) has been associated with detachment infected cells and eventually leads to vascular leakage haemorrhagic fever. Here we report that membrane-anchored GP is sufficient induce adherent cells. results show induced through either full-length GP1,2 or subunit GP2 depends cholesterol structure transmembrane domain. These data reveal a novel...