A5007341947- Receptor Mechanisms and Signaling
- Neuropeptides and Animal Physiology
- Cell Adhesion Molecules Research
- Monoclonal and Polyclonal Antibodies Research
- Mass Spectrometry Techniques and Applications
- Pancreatic function and diabetes
- Diabetes Treatment and Management
- Neuroendocrine Tumor Research Advances
- Protein Kinase Regulation and GTPase Signaling
- Cellular Mechanics and Interactions
- Virus-based gene therapy research
- Pancreatic and Hepatic Oncology Research
- RNA and protein synthesis mechanisms
- Hormonal and reproductive studies
- Adipose Tissue and Metabolism
- Biochemical Analysis and Sensing Techniques
- Nerve injury and regeneration
- Erythrocyte Function and Pathophysiology
- Hedgehog Signaling Pathway Studies
- Cholesterol and Lipid Metabolism
- Fibroblast Growth Factor Research
- Signaling Pathways in Disease
- Chemokine receptors and signaling
- S100 Proteins and Annexins
- Epigenetics and DNA Methylation
Leipzig University
2016-2025
University of Copenhagen
2014-2015
University Medical Center Hamburg-Eppendorf
2015
Novo Nordisk Foundation
2015
University of Amsterdam
2015
Universität Hamburg
2015
Johannes Gutenberg University Mainz
2015
Leiden University
2015
Friedrich-Alexander-Universität Erlangen-Nürnberg
2015
Vrije Universiteit Amsterdam
2015
Adhesion G protein-coupled receptors (aGPCRs) comprise the second largest yet least studied class of GPCR superfamily. aGPCRs are involved in many developmental processes and immune synaptic functions, but mode their signal transduction is unclear. Here, we show that a short peptide sequence (termed Stachel sequence) within ectodomain two (GPR126 GPR133) functions as tethered agonist. Upon structural changes receptor ectodomain, this intramolecular agonist exposed to seven-transmembrane...
The myelin sheath surrounding axons ensures that nerve impulses travel quickly and efficiently, allowing for the proper function of vertebrate nervous system. We previously showed adhesion G-protein-coupled receptor (aGPCR) Gpr126 is essential peripheral system myelination, although molecular mechanisms by which functions were incompletely understood. aGPCRs are a significantly understudied protein class, it was unknown whether couples to G-proteins. Here, we analyze Dhh(Cre);Gpr126(fl/fl)...
Adhesion GPCRs (aGPCRs) form the second largest, yet most enigmatic class of GPCR superfamily. Although physiologic importance aGPCRs was demonstrated in several studies, majority these receptors is still orphan with respect to their agonists and signal transduction. Recent studies reported that are activated through a tethered peptide agonist, coined Stachel sequence. The sequence C-terminal part highly conserved autoproteolysis-inducing domain. Here, we used cell culture-based assays...
Members of the adhesion G protein-coupled receptor (aGPCR) family carry an agonistic sequence within their large ectodomains. Peptides derived from this region, called Stachel sequence, can activate respective receptor. As conserved core region is highly similar between aGPCRs, agonist specificity sequence-derived peptides was tested members using cell culture-based second messenger assays. aGPCRs subfamily VI (GPR110/ADGRF1, GPR116/ADGRF5) and VIII (GPR64/ADGRG2, GPR126/ADGRG6) are able to...
The X-chromosomal GPR34 gene encodes an orphan Gi protein-coupled receptor that is highly conserved among vertebrates. To evaluate the physiological relevance of GPR34, we generated a GPR34-deficient mouse line. mice were vital, reproduced normally, and showed no gross abnormalities in anatomical, histological, laboratory chemistry, or behavioral investigations under standard housing. Because expressed mononuclear cells immune system, specifically tested for altered functions these cell...
Abstract Alternative splicing and multiple transcription start termination sites can produce a diverse repertoire of mRNA transcript variants from given gene. While the full picture human transcriptome is still incomplete, publicly available RNA datasets have enabled assembly transcripts. Using deep sequencing data 927 samples across 48 tissues, we quantified known new variants, provide an interactive, browser-based application Splice-O-Mat demonstrate its relevance using adhesion G...
Abstract Glucose homeostasis is maintained by hormones secreted from different cell types of the pancreatic islets and controlled manifold input including signals mediated through G protein-coupled receptors (GPCRs). RNA-seq analyses revealed expression numerous GPCRs in mouse human islets, among them Gpr116 / Adgrf5 . GPR116 an adhesion GPCR mainly found lung required for surfactant secretion. Here, we demonstrate that involved somatostatin release delta cells using a whole-body as well...
Abstract A large portion of the human GPCRome is still in dark and understudied, consisting even entire subfamilies GPCRs such as odorant receptors, class C orphans, adhesion GPCRs, Frizzleds taste receptors. However, it undeniable that these bring an untapped therapeutic potential should be explored further. Open questions on span diverse topics deorphanisation, development tool compounds tools for studying well understanding basic signalling mechanisms. This review gives overview current...
Abstract The enormous sizes of adhesion G protein-coupled receptors (aGPCRs) go along with complex genomic exon-intron architectures giving rise to multiple mRNA variants. There is a need for comprehensive catalog aGPCR variants proper evaluation the functions aGPCRs found in structural, vitro and animal model studies. We used an established bioinformatics pipeline extract, quantify visualize from deeply sequenced transcriptomes. Data analysis showed that have transcription start sites even...
G protein-coupled receptors (GPCR) are well-characterized regulators of a plethora physiological functions among them the modulation adipogenesis and adipocyte function. The class Adhesion GPCR (aGPCR) their role in adipose tissue, however, is poorly studied. With respect to demand for novel targets obesity treatment, we present comprehensive study on expression function this enigmatic during mature adipocytes.The all aGPCR representatives was determined by reanalyzing RNA-Seq data...
GPR133 (ADGRD1), an adhesion G protein–coupled receptor (GPCR) whose canonical signaling activates GαS-mediated generation of cytosolic cAMP, has been shown to be necessary for the growth glioblastoma (GBM), a brain malignancy. The extracellular N terminus is thought autoproteolytically cleaved into N-terminal and C- terminal fragments (NTF CTF, respectively). However, role this cleavage in activation remains unclear. Here, we used subcellular fractionation immunoprecipitation approaches...
G protein-coupled receptors (GPCRs) comprise an expanded superfamily of in the human genome. Adhesion class (adhesion-GPCRs) form second largest GPCRs. Despite abundance, size, molecular structure, and functions facilitating cell matrix contacts a variety organ systems, adhesion-GPCRs are by far most poorly understood GPCR class. Adhesion-GPCRs possess unique with extended N-termini containing various adhesion domains. In addition, many autoproteolytically cleaved into N-terminal fragment...
Cells respond to mechanical stimuli with altered signaling networks. Here, we show that forces rapidly induce phosphorylation of CD97/ADGRE5 (pCD97) at its intracellular C-terminal PDZ-binding motif (PBM). Biochemically, this disrupts CD97 binding PDZ domains the scaffold protein DLG1. In shear-stressed cells, pCD97 appears not only in junctions, retracting fibers, and attachment area but also lost membrane patches, demonstrating (intra)cellular detachment PBM. This is critical for...