A5050876763- Wnt/β-catenin signaling in development and cancer
- Cancer-related gene regulation
- Developmental Biology and Gene Regulation
- Sperm and Testicular Function
- Advanced Fluorescence Microscopy Techniques
- Lipid Membrane Structure and Behavior
- Neuropeptides and Animal Physiology
- Ubiquitin and proteasome pathways
- Receptor Mechanisms and Signaling
- Kruppel-like factors research
- Congenital heart defects research
- Force Microscopy Techniques and Applications
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Reproductive Biology and Fertility
- Connexins and lens biology
- Fibroblast Growth Factor Research
- Peptidase Inhibition and Analysis
- Heat shock proteins research
- Chemokine receptors and signaling
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Cell Adhesion Molecules Research
- Protein Kinase Regulation and GTPase Signaling
- Mitochondrial Function and Pathology
- Cancer, Stress, Anesthesia, and Immune Response
Max Planck Institute for the Science of Light
2019-2025
Friedrich-Alexander-Universität Erlangen-Nürnberg
2011-2024
Institute of Developmental Physiology
2020
Karlsruhe Institute of Technology
2003-2011
In-Q-Tel
2004
Hochschule Hannover
1999
University of Veterinary Medicine Hannover, Foundation
1997-1998
Wnt binding to members of the seven-span transmembrane Frizzled (Fz) receptor family controls essential cell fate decisions and tissue polarity during development in adulthood. The Fz-mediated membrane recruitment cytoplasmic effector Dishevelled (Dvl) is a critical step Wnt/β-catenin signaling initiation, but how Fz Dvl act together drive downstream events remains largely undefined. Here, we use an peptide-based microarray uncover mechanistically important role bipartite DEP domain C...
Abstract Connexins are the primary components of gap junctions, providing direct links between cells under many physiological processes. Here, we demonstrate that in addition to this canonical role, act as transcriptional regulators. We show Connexin 43 (Cx43) controls neural crest cell migration vivo by directly regulating N-cadherin transcription. This activity requires interaction Cx43 carboxy tail and basic transcription factor-3, which drives translocation nucleus. Once nucleus they...
Mitochondrial abundance is dynamically regulated and was previously shown to be increased by Wnt/β-catenin signaling. Pgam5 a mitochondrial phosphatase which cleaved the rhomboid protease presenilin-associated rhomboid-like protein (PARL) released from membranes after stress. In this study, we show that interacts with Wnt pathway component axin in cytosol, blocks axin-mediated β-catenin degradation, increases levels β-catenin–dependent transcription. stabilized inducing its dephosphorylation...
Transforming growth factor β (TGF-β) signaling is a core pathway of fibrosis, but the molecular regulation activation latent TGF-β remains incompletely understood. Here, we demonstrate crucial role WNT5A/JNK/ROCK that rapidly coordinates in fibrotic diseases. WNT5A was identified as predominant noncanonical WNT ligand diseases such systemic sclerosis, sclerodermatous chronic graft-versus-host disease, and idiopathic pulmonary stimulating fibroblast-to-myofibroblast transition tissue fibrosis...
The Wnt/beta-catenin signaling pathway is crucial for proper embryonic development and tissue homeostasis. phosphoprotein dishevelled (Dvl) an integral part of Wnt has recently been shown to interact with the multifunctional scaffolding protein beta-arrestin. Using Dvl deletion constructs, we found that beta-arrestin binds a region N-terminal PDZ domain Dvl, which contains casein kinase 1 (CK1) phosphorylation sites. Inhibition by CK1 inhibitors reduced binding Dvl. Moreover, mouse...
Lrp5/6 are crucial coreceptors for Wnt/β-catenin signaling, a pathway biochemically distinct from noncanonical Wnt signaling pathways. Here, we examined the possible participation of in signaling. We found that Lrp6 physically interacts with Wnt5a, but this does not lead to phosphorylation or activation pathway. Overexpression blocks Wnt5a downstream target Rac1, and effect is dependent on intact extracellular domains. These results suggested domain inhibits vitro. In vivo, Lrp6−/− mice...
Abstract Delivery of very small amounts reagents to the near-field cells with micrometer spatial precision and millisecond time resolution is currently out reach. Here we present μkiss as a micropipette-based scheme for brushing layer molecules nanoparticles onto live cell membrane from subfemtoliter confined volume perfusion flow. We characterize our system through both experiments modeling, find excellent agreement. demonstrate several applications that benefit controlled brush delivery,...
Dishevelled (Dvl) is a multifunctional effector of different Wnt cascades. Both canonical Wnt3a and noncanonical Wnt5a stimulate casein-kinase-1 (CK1) -mediated phosphorylation Dvl, visualized as electrophoretic mobility shift [phosphorylated shifted Dvl (ps-Dvl)]. However, the role this remains obscure. Here we report functional interaction ps-Dvl with receptor tyrosine kinase Ror2, which an alternative able to inhibit signaling. We demonstrate between Ror2 at cell membrane after or...
Amer1/WTX binds to the tumor suppressor adenomatous polyposis coli and acts as an inhibitor of Wnt signaling by inducing β-catenin degradation. We show here that Amer1 directly interacts with armadillo repeats via a domain consisting repeated arginine-glutamic acid-alanine (REA) motifs, assembles destruction complex at plasma membrane recruiting β-catenin, coli, Axin/Conductin. Deletion or specific mutations binding abolish its localization abrogate negative control signaling, which can be...
In many societies, the majority of adults regularly consume alcohol. However, only a small proportion develops alcohol addiction. Individuals at risk often show high sensation-seeking/low-anxiety behavioural phenotype. Here we asked which role EF hand domain containing 2 (EFhd2; Swiprosin-1) plays in control addiction-associated behaviours. EFhd2 knockout (KO) mice drink more than controls and spontaneously escalate their consumption. This coincided with sensation-seeking low-anxiety A...
Abstract Background Bone morphogenetic proteins regulate multiple processes in embryonic development, including early dorso-ventral patterning and neural crest development. BMPs activate heteromeric receptor complexes consisting of type I II receptor-serine/threonine kinases. BMP receptors Ia Ib, also known as ALK3 ALK6 respectively, are the most common that likely mediate signaling events. Since expression patterns functions Xenopus laevis development have not been described, we addressed...
Hepatocellular carcinoma (HCC) is clearly age-related and represents one of the deadliest cancer types worldwide. As a result globally increasing risk factors including metabolic disorders, incidence rates HCC are still rising. However, molecular hallmarks remain poorly understood. Neuropeptide Y (NPY) NPY receptors represent highly conserved, stress-activated system involved in diverse cancer-related aging alterations, but its impact on liver had been unclear. Here, we observed increased...
Abstract Microproteins, short functional peptides encoded by small genes, are emerging as critical regulators of cellular processes, yet their roles in mitochondrial function and neurodegeneration remain underexplored. In this study, we identify NCBP2-AS2 an evolutionarily conserved microprotein with significant energy metabolism neurogenesis. Using a combination molecular approaches, including CRISPR/Cas9 knockout models, stoichiometric co- immunoprecipitation, advanced imaging techniques,...
Liver metastasis development in breast cancer patients is common and confers a poor prognosis. So far, the prognostic significance of surgical resection clinical relevance biomarker analysis metastatic tissue have barely been investigated. We previously demonstrated an impact WNT signaling brain metastasis. This study aimed to investigate value established markers components liver metastases. Overall N = 34 metastases (with matched primaries 19/34 cases) were included this retrospective...
Dishevelled (DVL) is the key component of Wnt signaling pathway. Currently, DVL conformational dynamics under native conditions unknown. To overcome this limitation, we develop Fluorescein Arsenical Hairpin Binder- (FlAsH-) based FRET in vivo approach to study conformation living cells. Using single-cell approach, demonstrate that (i) ligands induce open conformation, (ii) variants are predominantly open, show more even subcellular localization and efficient membrane recruitment by Frizzled...