Protein Traffic Disorders: An Effective High-Throughput Fluorescence Microscopy Pipeline for Drug Discovery

Scientific Reports

Volumn 5, Issue , 2015, Pages

  Botelho, Hugo M ^a,b   Uliyakina, Inna ^a,b   Awatade, Nikhil T ^a   Proenҫa, Maria C ^a   Tischer, Christian ^b   Sirianant, Lalida ^c   Kunzelmann, Karl ^c   Pepperkok, Rainer ^b   Amaral, Margarida D ^a  

^a UNIVERSITY OF LISBON   (Portugal)

^b EUROPEAN MOLECULAR BIOLOGY LABORATORY   (Germany)

^c UNIVERSITY OF REGENSBURG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; MEMBRANE PROTEIN; MOLECULAR LIBRARY; SMALL INTERFERING RNA;

CELL LINE; DRUG DEVELOPMENT; FLUORESCENCE MICROSCOPY; GENE EXPRESSION; GENE LIBRARY; GENETICS; HIGH THROUGHPUT SCREENING; HUMAN; METABOLISM; MOLECULAR LIBRARY; MUTATION; PATCH CLAMP TECHNIQUE; PROCEDURES; PROTEIN TRANSPORT; REPORTER GENE;

CELL LINE; CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR; DRUG DISCOVERY; GENE EXPRESSION; GENE LIBRARY; GENES, REPORTER; HIGH-THROUGHPUT SCREENING ASSAYS; HUMANS; MEMBRANE PROTEINS; MICROSCOPY, FLUORESCENCE; MUTATION; PATCH-CLAMP TECHNIQUES; PROTEIN TRANSPORT; RNA, SMALL INTERFERING; SMALL MOLECULE LIBRARIES;

EID: 84924871406     PISSN: None     EISSN: 20452322     Source Type: Journal    
DOI: 10.1038/srep09038     Document Type: Article

References (47)

1. Fagerberg, L., Jonasson, K., von Heijne, G., Uhlen, M. & Berglund, L. Prediction of the human membrane proteome. Proteomics 10, 1141-1149 (2010).
2. Aridor, M. Visiting the ER: the endoplasmic reticulum as a target for therapeutics in traffic related diseases. Adv. Drug Deliv. Rev. 59, 759-781 (2007).
3. De Matteis, M. A. & Luini, A. Mendelian disorders of membrane trafficking. N. Engl. J. Med. 365, 927-938 (2011).
4. Hutt, D. M., Powers, E. T. & Balch, W. E. The proteostasis boundary in misfolding diseases of membrane traffic. FEBS Lett. 583, 2639-2646 (2009).
5. Denning, G. M., Ostedgaard, L. S. & Welsh, M. J. Abnormal localization of cystic fibrosis transmembrane conductance regulator in primary cultures of cystic fibrosis airway epithelia. J. Cell Biol. 118, 551-559 (1992).
6. Wesche, D., Deen, P. M. & Knoers, N. V. Congenital nephrogenic diabetes insipidus: the current state of affairs. Pediatr. Nephrol. 27, 2183-2204 (2012).
7. Oetting, W. S. The tyrosinase gene and oculocutaneous albinism type 1 (OCA1):A model for understanding the molecular biology of melanin formation. Pigment Cell Res. 13, 320-325 (2000).
8. Lubrano-Berthelier, C. et al. Intracellular retention is a common characteristic of childhood obesity-associated MC4R mutations. Hum. Mol. Genet. 12, 145-153 (2003).
9. Sung, C. H., Davenport, C.M. & Nathans, J. Rhodopsin mutations responsible for autosomal dominant retinitis pigmentosa. Clustering of functional classes along the polypeptide chain. J. Biol. Chem. 268, 26645-26649 (1993).
10. Newton, C. L. et al. Rescue of expression and signaling of human luteinizing hormone G protein-coupled receptor mutants with an allosterically binding small-molecule agonist. Proc. Natl. Acad. Sci. U. S. A. 108, 7172-7176 (2011).
11. Strom, T. B., Tveten, K., Laerdahl, J. K. & Leren, T. P. Mutation G805R in the transmembrane domain of the LDL receptor gene causes familial hypercholesterolemia by inducing ectodomain cleavage of the LDL receptor in the endoplasmic reticulum. FEBS Open Bio 4, 321-327 (2014).
12. Gooptu, B., Dickens, J. A. & Lomas, D. A. Themolecular and cellular pathology of alpha1-antitrypsin deficiency. Trends Mol. Med. 20, 116-127 (2014).
13. De Matteis, M. A., Vicinanza, M., Venditti, R. & Wilson, C. Cellular assays for drug discovery in genetic disorders of intracellular trafficking. Annu. Rev. Genomics Hum. Genet. 14, 159-190 (2013).
14. Riordan, J. R. et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA. Science 245, 1066-1073 (1989).
15. Amaral, M. D. CFTR and chaperones: processing and degradation. J. Mol. Neurosci. 23, 41-48 (2004).
16. Dalemans, W. et al. Altered chloride ion channel kinetics associated with the delta F508 cystic fibrosis mutation. Nature 354, 526-528 (1991).
17. Moniz, S. et al. HGF stimulation of Rac1 signaling enhances pharmacological correction of the most prevalent cystic fibrosismutant F508del-CFTR. ACS Chem. Biol. 8, 432-442 (2013).
18. Almac¸a, J. et al. High-content siRNA screen reveals global ENaC regulators and potential cystic fibrosis therapy targets. Cell 154, 1390-1400 (2013).
19. Accurso, F. J. et al. Effect of VX-770 in persons with cystic fibrosis and the G551D-CFTR mutation. N. Engl. J. Med. 363, 1991-2003 (2010).
20. De Boeck, K., Pasakavitz, J., Chen, X. & Higgins, M. Ivacaftor, a CFTR potentiator, in cystic fibrosis patients who have a non-G551D-CFTR gating mutation: phase 3, part 1 results. Pediatr. Pulmonol. 48, 292 (2013).
21. Van Goor, F. et al. Correction of the F508del-CFTR protein processing defect in vitro by the investigational drug VX-809. Proc. Natl. Acad. Sci. U. S. A. 108, 18843-18848 (2011).
22. Clancy, J. P. et al. Results of a phase IIa study of VX-809, an investigational CFTR corrector compound, in subjects with cystic fibrosis homozygous for the F508del- CFTR mutation. Thorax 67, 12-18 (2012).
23. Almac¸a, J. et al. Functional genomics assays to study CFTR traffic and ENaC function. Methods Mol. Biol. 742, 249-264 (2011).
24. Ehrhardt, C. et al. Towards an in vitro model of cystic fibrosis small airway epithelium: characterisation of the human bronchial epithelial cell line CFBE41o. Cell Tissue Res. 323, 405-415 (2006).
25. Erfle, H. et al. Work flow for multiplexing siRNA assays by solid-phase reverse transfection in multiwell plates. J. Biomol. Screen. 13, 575-580 (2008).
26. Pedemonte, N., Zegarra-Moran, O. & Galietta, L. J. High-throughput screening of libraries of compounds to identify CFTR modulators. Methods Mol. Biol. 741, 13-21 (2011).
27. Holleran, J. et al. Fluorogen-activating proteins as biosensors of cell-surface proteins in living cells. Cytometry A 77, 776-782 (2010).
28. Holleran, J. P., Zeng, J., Frizzell, R. A. & Watkins, S. C. Regulated recycling of mutant CFTR is partially restored by pharmacological treatment. J. Cell Sci. 126, 2692-2703 (2013).
29. Holleran, J. P. et al. Pharmacological rescue of the mutant cystic fibrosis transmembrane conductance regulator (CFTR) detected by use of a novel fluorescence platform. Mol. Med. 18, 685-696 (2012).
30. Galietta, L. V., Jayaraman, S. & Verkman, A. S. Cell-based assay for highthroughput quantitative screening of CFTR chloride transport agonists. Am. J. Physiol. Cell Physiol. 281, C1734-1742 (2001).
31. Pedemonte, N. et al. Small-molecule correctors of defective DeltaF508-CFTR cellular processing identified by high-throughput screening. J. Clin. Invest. 115, 2564-2571 (2005).
32. Fahy, J. V. & Dickey, B. F. Airway mucus function and dysfunction. N. Engl. J. Med. 363, 2233-2247 (2010).
33. Iwashita, H., Fujimoto, K.,Morita, S., Nakanishi, A. & Kubo, K. Increased human Ca(2)(+)-activated Cl(+) channel 1 expression and mucus overproduction in airway epithelia of smokers and chronic obstructive pulmonary disease patients. Respir. Res. 13, 55 (2012).
34. Rock, J. R. et al. Transmembrane protein 16A (TMEM16A) is a Ca2+-regulated Cl- secretory channel in mouse airways. J. Biol. Chem. 284, 14875-14880 (2009).
35. Moskowitz, S. M., Chmiel, J. F., Sternen, D. L., Cheng, E. & Cutting, G. R. in GeneReviews (eds Pagon, R. A. et al) (1993).
36. Amaral, M. D. & Farinha, C. M. Rescuing mutant CFTR: amulti-task approach to a better outcome in treating cystic fibrosis. Curr. Pharm. Des. 19, 3497-3508 (2013).
37. Noone, P. G. & Knowles, M. R. 'CFTR-opathies': disease phenotypes associated with cystic fibrosis transmembrane regulator gene mutations. Respir. Res. 2, 328-332 (2001).
38. Dransfield, M. T. et al. Acquired cystic fibrosis transmembrane conductance regulator dysfunction in the lower airways in COPD. Chest 144, 498-506 (2013).
39. Su, X. et al. Role of CFTR expressed by neutrophils in modulating acute lung inflammation and injury in mice. Inflamm. Res. 60, 619-632 (2011).
40. Factor, P. et al. Adenosine regulation of alveolar fluid clearance. Proc. Natl. Acad. Sci. U. S. A. 104, 4083-4088 (2007).
41. Luciani, A. et al. Defective CFTR induces aggresome formation and lung inflammation in cystic fibrosis through ROS-mediated autophagy inhibition. Nat. Cell Biol. 12, 863-875 (2010).
42. Tsukaguchi, H. et al. Binding-, intracellular transport-, and biosynthesis-defective mutants of vasopressin type 2 receptor in patients with X-linked nephrogenic diabetes insipidus. J. Clin. Invest. 96, 2043-2050 (1995).
43. Brown, M. S. & Goldstein, J. L. A receptor-mediated pathway for cholesterol homeostasis. Science 232, 34-47 (1986).
44. Amara, J. F., Cheng, S. H. & Smith, A. E. Intracellular protein trafficking defects in human disease. Trends Cell Biol. 2, 145-149 (1992).
45. Erfle, H. et al. Reverse transfection on cell arrays for high content screening microscopy. Nat. Protoc. 2, 392-399 (2007).
46. Neumann, B. et al.High-throughput RNAi screening by time-lapse imaging of live human cells. Nat. Methods 3, 385-390 (2006).
47. Simpson, J. C. et al.Genome-wide RNAi screening identifies human proteins with a regulatory function in the early secretory pathway. Nat. Cell Biol. 14, 764-774 (2012).