Real-time imaging of Notch activation with a luciferase complementation-based reporter

Science Signaling

Volumn 4, Issue 181, 2011, Pages

  Ilagan, Ma Xenia G ^a   Lim, Sora ^a   Fulbright, Mary ^a   Piwnica Worms, David ^a,b   Kopan, Raphael ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ADAM PROTEIN; DNA BINDING PROTEIN; GAMMA SECRETASE; LUCIFERASE; NOTCH RECEPTOR; MUSCLE PROTEIN; SECRETASE; SMPX PROTEIN, MOUSE;

ANIMAL CELL; ARTICLE; CELL MATURATION; CELL RENEWAL; CONTROLLED STUDY; GENETIC COMPLEMENTATION; HIGH THROUGHPUT SCREENING; LIGAND BINDING; LUCIFERASE COMPLEMENTATION IMAGING; MAMMAL CELL; MOLECULAR IMAGING; NONHUMAN; PHARMACODYNAMICS; PRIORITY JOURNAL; REPORTER GENE; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION; ACTIVE TRANSPORT; ANIMAL; CELL NUCLEUS; CELL STRAIN 3T3; CHO CELL; CRICETULUS; GENE EXPRESSION REGULATION; GENETICS; HAMSTER; METABOLISM; METHODOLOGY; MOUSE; MOUSE MUTANT; PHYSIOLOGY; PROTEIN TERTIARY STRUCTURE;

MAMMALIA;

3T3 CELLS; ACTIVE TRANSPORT, CELL NUCLEUS; ADAM PROTEINS; AMYLOID PRECURSOR PROTEIN SECRETASES; ANIMALS; CELL NUCLEUS; CHO CELLS; CRICETINAE; CRICETULUS; GENE EXPRESSION REGULATION; GENES, REPORTER; GENETIC COMPLEMENTATION TEST; LUCIFERASES; MICE; MICE, KNOCKOUT; MUSCLE PROTEINS; PROTEIN STRUCTURE, TERTIARY; RECEPTORS, NOTCH; SIGNAL TRANSDUCTION;

EID: 79960360048     PISSN: 19450877     EISSN: 19379145     Source Type: Journal    
DOI: 10.1126/scisignal.2001656     Document Type: Article

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67. Acknowledgments: We would like to thank our colleagues for providing various reagents: J. Aster, I. Bernstein, S. Chiba, S. Egan, M. Freeman, T. Golde, J. Griffin, D. Hayward, H. Hirai, T. Honjo, A. Israel, R. Kageyama, K. Murphy, W. Pear, and H. Piwnica-Worms, as well as Merck. We thank members of the Piwnica-Worms and Kopan laboratories for discussions and technical assistance, especially C. Ong for preparing the Dll1-Fc and control constructs. We thank B. Nolan (Chemical Genetics Screening Core) and J. Marasa (Molecular Imaging Center High Throughput Screening Core) for their assistance in adapting the Notch-LCI assay for automation and HTS. We also thank D. Oakley (Bakewell NeuroImaging Laboratory) for his assistance with the cellular bioluminescence imaging. We acknowledge S. Chen and M. Hass, G. Zhao, and C. Sato for their critical reading of the manuscript. Funding: Support for this work was provided by grants from the NIH: a Neuroscience Blueprint Core Grant P30 NS057105 (Washington University), R21-NS06168001 (M.X.G.I.), AG025973P50 (R.K.), CA94056 (D.P.-W.), and P50 AG005681 (J. Morris). Author contributions: M.X.G.I., D.P.-W., and R.K. conceptualized the project and designed the experiments. M.X.G.I. designed and performed most of the experiments and data analyses. S.L. performed some experiments and analyzed the data. M.F. prepared many of the constructs described herein. M.X.G.I., D.P.-W., and R.K. contributed new reagents and analytical tools. M.X.G.I. and R.K. wrote the paper, with input from all co-authors. Competing interests: M.X.G.I., D.P.-W., R.K., and Washington University may receive income based on a license of Notch-related technology by the university to Merck. Merck did not support this work. A standard academic material transfer agreement (MTA) applies for the Notch-LCI reporter expression plasmids and stable cell lines. D.P.-W. and Washington University hold a patent on the split luciferase (US 7,442,518), but no restrictions apply for academic researchers.