PROJEKT C1

Untersuchung der räumlichen Anordnung und Dynamik von G-Protein-gekoppelten Rezeptoren durch Einzelmolekül- und Superresolution-Mikroskopie

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G-Protein gekoppelte Rezeptoren (GPCRs) bilden die größte Familie von Rezeptoren für Hormone und Neurotransmitter und repräsentieren wichtige pharmakologische Ziele. Um die Lokalisierung von GPCRs in dynamischen Nanodomänen auf der Zelloberfläche zu untersuchen, verwenden wir in diesem Projekt neue optische Verfahren wie Einzelmolekül- und hochauflösende Mikroskopie (dSTORM). Unsere Experimente erlauben ein tieferes Verständnis grundlegender Mechanismen von GPCR Signalwegen und können zu innovativen Medikamenten für eine Vielzahl von Krankheiten führen.

Titel Jahr Autoren Journal Links
Internalized TSH receptors en route to the TGN induce local Gs-protein signaling and gene transcription 2017 Godbole, A., Lyga, S., Lohse, M. J., and Calebiro, D. Nat Comm More
Single-molecule imaging reveals receptor-G protein interactions at cell surface hot spots 2017 Sungkaworn, T., Jobin, M.-L., Burnecki, K., Weron, A., Lohse, M. J., and Calebiro, D. Nature More
cAMP Signals in Drosophila Motor Neurons Are Confined to Single Synaptic Boutons 2016 Maiellaro, I., Lohse, M. J., Kittel, R. J. and Calebiro, D. Cell Rep More
Constitutive activation of PKA catalytic subunit in adrenal Cushing’s syndrome 2014 Beuschlein, F., Fassnacht, M., Assié, G., Calebiro, D., Stratakis, C. A., Osswald, A., Ronchi, C. L., Wieland, T., Sbiera, S., Faucz, F. R., Schaak, K., Schmittfull, A., Schwarzmayr, T., Barreau, O., Vezzosi, D., Rizk-Rabin, M., Zabel, U., Szarek, E., Salpea, P., Forlino, A., Vetro, A., Zuffardi, O., Kisker, C., Diener, S., Meitinger, T., Lohse, M. J., Reincke, M., Bertherat, J., Strom, T. M., and Allolio, B. N Engl J Med More
High-resolution Spatiotemporal Analysis of Receptor Dynamics by Single-molecule Fluorescence Microscopy 2014 Sungkaworn, T., Rieken, F., Lohse, M. J., and Calebiro, D. J Vis Exp More
Single-molecule analysis of fluorescently labeled G-protein-coupled receptors reveals complexes with distinct dynamics and organization 2013 Calebiro, D., Rieken, F., Wagner, J., Sungkaworn, T., Zabel, U., Borzi, A., Cocucci, E., Zurn, A., and Lohse, M. J. Proc Natl Acad Sci USA More
Persistent cAMP signaling by inter- nalized TSH receptors occurs in thyroid but not in HEK293 cells 2012 Werthmann, R. C., Volpe, S., Lohse, M. J., and Calebiro, D. FASEB J More
Frequent TSH receptor genetic alterations with variable signaling impairment in a large series of children with nonautoimmune isolated hyperthyrotropinemia 2012 Calebiro, D., Gelmini, G., Cordella, D., Bonomi, M., Winkler, F., Biebermann, H., de Marco, A., Marelli, F., Libri, D. V., Antonica, F., Vigone, M. C., Cappa, M., Mian, C., Sartorio, A., Beck-Peccoz, P., Radetti, G., Weber, G., and Persani, L. J Clin Endocrinol Metab More
FRET measurements of intracellular cAMP concentrations and cAMP analog permeability in intact cells 2011 Börner, S., Schwede, F., Schlipp, A., Berisha, F., Calebiro, D., Lohse, M. J., and Nikolaev, V. O. Nat Protoc More
Real-time monitoring of somatostatin receptor-cAMP signaling in live pituitary 2010 Jacobs, S., Calebiro, D., Nikolaev, V. O., Lohse, M. J., and Schulz, S. Endocrinology More
Persistent cAMP-signals triggered by internalized G-protein-coupled receptors 2009 Calebiro, D., Nikolaev, V. O., Gagliani, M. C., de Filippis, T., Dees, C., Tacchetti, C., Persani, L., and Lohse, M. J. PLoS Biol More
Selective modulation of protein kinase A I and II reveals distinct roles in thyroid cell gene expression and growth 2006 Calebiro, D., de Filippis, T., Lucchi, S., Martinez, F., Porazzi, P., Trivellato, R., Locati, M., Beck-Peccoz, P., and Persani, L. Mol Endocrinol More
Intracellular entrapment of wild-type TSH receptor by oligomerization with mutants linked to dominant TSH resistance 2005 Calebiro, D., de Filippis, T., Lucchi, S., Covino, C., Panigone, S., Beck-Peccoz, P., Dunlap, D., and Persani, L. Hum Mol Genet More