GPCR; Rab GTPases; Receptor signaling; VEGFR2; Receptor trafficking; Angiogenesis; Receptor endocytosis
Xie Ye, Mansouri Maysam, Rizk Aurélien, Berger Philipp (2019), Regulation of VEGFR2 trafficking and signaling by Rab GTPase-activating proteins, in Scientific Reports
, 9(1), 13342-13342.
Mansouri Maysam, Berger Philipp (2018), Multigene delivery in mammalian cells: Recent advances and applications, in Biotechnology Advances
Mansouri Maysam, Ehsaei Zahra, Taylor Verdon, Berger Philipp (2017), Baculovirus-based genome editing in primary cells, in Plasmid
, 90, 5-9.
Mansouri Maysam, Bellon-Echeverria Itxaso, Rizk Aurélien, Ehsaei Zahra, Cianciolo Cosentino Chiara, Silva Catarina S., Xie Ye, Boyce Frederick M., Davis M. Wayne, Neuhauss Stephan C. F., Taylor Verdon, Ballmer-Hofer Kurt, Berger Imre, Berger Philipp (2016), Highly efficient baculovirus-mediated multigene delivery in primary cells, in Nature Communications
, 7, 11529-11529.
Mansouri Maysam, Berger Philipp (2014), Strategies for multigene expression in eukaryotic cells., in Plasmid
, 5, 12-1.
Receptor tyrosine kinases (RTKs) and G protein coupled receptors (GPCRs) are key components of cell physiology since they transmit signals from the outside to the cytoplasm of cells. Receptor tyrosine kinases possess a single transmembrane domain and are mainly involved in organism forming processes such as cell proliferation and differentiation. GPCRs are seven transmembrane domain receptors that modulate a wide variety of physiological processes including blood pressure, inflammation and mood. Both receptor families are consequently attractive targets for pharmaceutical companies. Ligand binding initiates signal transmission, internalization, and trafficking of the receptor. Recent studies have revealed that distinct isoforms of growth factors or some synthetic ligands activate only a part of the signaling pathways when compared with full agonists, and promote alternative trafficking routes within the cell, a process called biased signaling. Understanding this process is extremely important for drug development, since it could allow the optimization of the signaling outcome and drug response. In an ideal case, therapeutic effects associated with a particular signaling pathway could be separated from unwanted side effects caused by the activation of additional signaling pathways.The following topics will be addressed:A. New strategies to interfere with angiogenic signalingVEGF-A165a, one of the main drivers of tumor angiogenesis, leads to a different trafficking of VEGFR2 than does VEGF-A165b, which has only weak angiogenic potential. Interfering with VEGFR2 trafficking may therefore represent a new approach to prevent pathological angiogenesis in diseases such as cancer and macula degeneration.B. Trafficking of psychosis-related heterodimeric GPCR complexes.Hallucinogenic drugs act in vivo on the serotonin receptor type 2A (5-HT2A), which forms heterodimeric complexes with the metabotropic glutamate receptor 2 (mGluR2) or the dopamine receptor D2 (D2DR). We compare the influence of hallucinogenic and nonhallucinogenic drugs on receptor recycling and degradation, because the levels of these receptors are altered in schizophrenic patients. C. High resolution map of intracellular trafficking routesIntracellular receptor trafficking routes are currently not defined at high resolution. We will generate a high resolution map using Rab GTPases as markers.Scientific value: It becomes more and more evident that it is possible to identify ligands that activate only part of the signaling pathways of a particular receptor. These ligands are clinically extremely interesting. Most studies focus on the signalling output of the ligand / receptor complex, because the corresponding high-throughput technologies are established. We will focus on the dynamic distribution of receptors within cells, thereby creating novel complementary datasets for pharmacological intervention.