A5062049260- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Circadian rhythm and melatonin
- RNA Interference and Gene Delivery
- Receptor Mechanisms and Signaling
- Advanced biosensing and bioanalysis techniques
- Advanced Fluorescence Microscopy Techniques
- Virus-based gene therapy research
- Cancer-related Molecular Pathways
- Peptidase Inhibition and Analysis
- Neuroendocrine regulation and behavior
- Developmental Biology and Gene Regulation
- Ubiquitin and proteasome pathways
- Galectins and Cancer Biology
- Estrogen and related hormone effects
- Hypothalamic control of reproductive hormones
- Cellular Mechanics and Interactions
- Birth, Development, and Health
- Pluripotent Stem Cells Research
- Growth Hormone and Insulin-like Growth Factors
- Cellular transport and secretion
- Neuropeptides and Animal Physiology
- Genetic and Kidney Cyst Diseases
- Neurobiology and Insect Physiology Research
- Regulation of Appetite and Obesity
Karlsruhe Institute of Technology
2012-2024
Screen
2024
DKFZ-ZMBH Alliance
2001-2009
German Cancer Research Center
2002-2009
Heidelberg University
2001-2009
European Molecular Biology Laboratory
1997-2007
MRC Laboratory of Molecular Biology
2007
VA Connecticut Healthcare System
2004
European Molecular Biology Organization
2001
European Molecular Biology Laboratory
1999
Multiple signaling pathways, including Wnt signaling, participate in animal development, stem cell biology, and human cancer. Although many components of the pathway have been identified, unresolved questions remain as to mechanism by which binding its receptors Frizzled Low-density lipoprotein receptor-related protein 6 (LRP6) triggers downstream events. With live imaging vertebrate cells, we show that treatment quickly induces plasma membrane-associated LRP6 aggregates. aggregates are...
Abstract The functional significance of the pars tuberalis (PT) mammalian adenohypophysis has remained an enigma (1, 2). One view its function is that it acts as auxiliary gland to support endocrine role distalis (PD) (2), been shown contain immunocytochemically identifiable thyrotrophs and gonadotrophs (1). Many cells PT are, however, ultrastructurally unique suggesting independent for this tissue. Our recent demonstration rat a major binding site ligand iodomelatonin lends further idea...
A gradient of Wnt/beta-catenin signalling formed by posteriorising Wnts and anteriorising Wnt antagonists regulates anteroposterior (AP) patterning the central nervous system (CNS) during Xenopus gastrulation. In this process, secreted antagonist Dkk1 functions in Spemann organiser its anterior derivatives blocking receptors lipoprotein receptor-related protein (LRP) 5 6 class. addition to LRP6, interacts with another recently identified receptor class, transmembrane proteins Kremen1 (Krm1)...
ABSTRACT Primary cultures of ovine pars tuberalis (PT) cells the pituitary were established to investigate mode action melatonin. The heterogeneous population was shown bind radioligand 2-[ 125 I]-melatonin over 72 h in culture, although there a progressive decline specific binding with time. In cultured for 24 h, forskolin (1 μmol/l) found stimulate 12-fold increase cyclic AMP accumulation. This response could be inhibited by melatonin dose-dependent manner, an IC 50 approx. 6 pmol/l....
Abstract A high-affinity, discretely localized melatonin receptor has been characterized and mapped within the brain pituitary of Syrian hamster using high specific activity ligand [(125)|]iodomelatonin a combination in vitro autoradiography membrane homogenate assays. Specific binding radioligand was found regions epithalamus hypothalamus pars tuberalis pituitary. Excitatory amino-acid lesions destroyed brain, demonstrating that sites are located on neurons. Analysis to homogenates revealed...
The effect of guanine nucleotides and related analogues on the binding 2-[125I]-melatonin to membranes prepared from ovine pars tuberalis was studied. Dose-dependent inhibition observed, with an order potency GTPγS > Gpp(NH)p GTP = GDP. GMP, cyclic GMP ATP had negligible effects. Analysis saturable revealed that (1 µM) promoted apparent reduction in receptor density about 50%, without a concomitant change affinity. These results are consistent melatonin existing equilibrium between high-...
Artificial multicellular systems are gaining importance in the field of tissue engineering and regenerative medicine. Reconstruction complex architectures vitro is nevertheless challenging, methods permitting controllable high-throughput fabrication needed. Here, a facile method developed based on tunable droplet-fusion technique, allowing programmed assembly multiple cell spheroids into architectures. The technique allows for construction various (double-spheroids, multi-spheroids,...
ABSTRACT A new member of the G protein-coupled receptor superfamily has been isolated from an ovine genomic library with a probe generated by application PCR technique, using cDNA synthesized on mRNA template pars tuberalis. This clone encodes novel 325 amino acids seven transmembrane domains. These domains share homology other members this family, but best is recently cloned human MC-1 (50% in domains) and MC-3 (69% MSH receptors ACTH (42% receptor. When was expressed Cos7 cells, it able to...
After activation by Wnt/β-Catenin ligands, a multi-protein complex assembles at the clustering membrane-bound receptors and intracellular signal transducers into so-called Lrp6-signalosome. However, mechanism of signalosome formation dissolution is yet not clear. Our imaging studies live zebrafish embryos show that highly dynamic structure. It continuously assembled Dvl2-mediated recruitment transducer to activated partially disassembled endocytosis. We find that, after internalization,...
Growth factor antagonists play important roles in mediating the inductive effects of Spemann organizer amphibian embryos and its equivalents other vertebrates. Dual inhibition Wnt BMP signals has been proposed to confer head activity. We tested requirement this coinhibition Xenopus mice. In Xenopus, simultaneous reduction chordin noggin, antagonist dickkopf1 (dkk1) leads anterior truncations. mice, compound mutants for dkk1 noggin display severe defects, with deletion all structures...
Bordetella pertussis toxin (islet activating protein, IAP) has been used to investigate the G‐proteins involved in mediating action of melatonin receptor. Melatonin inhibits iorskolin‐stimulated cyclic AMP production ovine pars tuberalis (PT) cells. In cells treated with IAP for 16 h this response is attenuated a dose‐dependent manner, but not abolished. catalyses incorporation [ 32 P‐ADP]ribose into 41 kd protein present PT membranes, labelling can be reduced if are preincubated h....
The Wingless/Int1 (Wnt) signaling system plays multiple, essential roles in embryonic development, tissue homeostasis, and human diseases. Although many of the underlying mechanisms are becoming clearer, binding mode, kinetics, selectivity 19 mammalian WNTs to their receptors class Frizzled (FZD1–10) remain obscure. Attempts investigate Wnt-FZD interactions hampered by difficulties working with Wnt proteins recalcitrance epitope tagging. Here, we used a fluorescently tagged version mouse...
The WNT signaling system governs critical processes during embryonic development and tissue homeostasis, its dysfunction can lead to cancer. Details concerning selectivity differences in relative binding affinities of 19 mammalian WNTs the cysteine-rich domain (CRD) their receptors-the ten Frizzleds (FZDs)-remain unclear. Here, we used eGFP-tagged mouse WNT-3A for a systematic analysis interaction with every human FZD paralogue HEK293A cells. Employing HiBiT-tagged full-length FZDs, studied...
The Mel 1a receptor gene has recently been cloned and sequenced, its product found to represent a new class of the G protein-coupled superfamily. A unique aspect endogenous hormonal ligand, melatonin, is prolonged duration (16 h) required initiate appropriate photoperiodic responses in animal. This study provides first data on transcriptional translational regulation this primary cultures native tissue, pars tuberalis ovine pituitary. Using RNAse protection assays we show mRNA expression...
Abstract Background A fundamental requirement for development of diverse brain regions is the function local organizers at morphological boundaries. These are restricted groups cells that secrete signaling molecules, which in turn regulate fate adjacent neural tissue. The thalamus located caudal diencephalon and central relay station between sense organs higher areas. mid-diencephalic organizer ( MDO ) orchestrates by releasing secreted molecules such as Shh. Results Here we show canonical...