An αB-Crystallin Peptide Rescues Compartmentalization and Trafficking Response to Cu Overload of ATP7B-H1069Q, the Most Frequent Cause of Wilson Disease in the Caucasian Population
Abstract
:1. Introduction
2. Results
2.1. The α-Crystallin Domain of CRYAB Rescues Golgi Localization of the ATP7B-H1069Q Mutant
2.2. Internalization and Distribution of Pept 73–92 in COS7 Cells
2.3. Pept 73–92 Specifically Rescues Golgi Localization of ATB7B-H1069Q
2.4. ATP7B-H1069Q Localized in the Golgi Complex Thanks to Pept 73–92 Moves to Post-Golgi Vesicles in Response to Cu Overload
2.5. Pept 73–92 Interacts with ATP7B-H1069Q
3. Discussion
4. Materials and Methods
4.1. cDNA Cloning and Plasmid Construction
- N-terminal domain
- FW: 5′-GAATTCATGGACATCGCCATCCACC-3′
- REV: 5′-CTCGAGCTATGAGAGAGTCCAGTGTCAAACC-3′
- α-crystallin domain
- FW: 5′-GAATTCCTCTCAGAGATGCGCCTGG-3′
- REV: 5′-CTCGAGCTAATTCACAGTGAGGACCC-3′
- C-terminal domain
- FW: 5′-GAATTCCCAAGGAAACAGGTCTCTG-3′
- REV: 5′-CTCGAGCTATTTCTTGGGGGCTGC-3’
4.2. Cell Culture, Transfection, MTT Assay, Cell Fractionation and Immunoprecipitation
4.3. Peptides
4.4. Immunofluorescence
4.5. Mass Spectrometry Analysis
4.6. FLIM-FRET Analysis
4.7. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Acknowledgements
Conflicts of interest
Abbreviations
WD | Wilson Disease |
TGN | Trans-Golgi Network |
ER | Endoplasmic Reticulum |
CRYAB | αB-Crystallin |
GFP | Green Fluorescent Protein |
HA | Hemagglutinin |
ACD | α-Crystallin Domain |
NTD | N-Terminal Domain |
CTD | C-Terminal Domain |
TAMRA | Tetramethylrhodamine Azide |
MTT | 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide |
FLIM | Fluorescence Lifetime Imaging Microscopy |
FRET | Fluorescence Resonance Energy Transfer |
References
- Coffey, A.J.; Durkie, M.; Hague, S.; McLay, K.; Emmerson, J.; Lo, C.; Klaffke, S.; Joyce, C.J.; Dhawan, A.; Hadzic, N.; et al. A genetic study of Wilson’s disease in the United Kingdom. Brain 2013, 136 Pt 5, 1476–1487. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jang, J.H.; Lee, T.; Bang, S.; Kim, Y.E.; Cho, E.H. Carrier frequency of Wilson’s disease in the Korean population: A DNA-based approach. J. Hum. Genet. 2017, 62, 815–818. [Google Scholar] [CrossRef] [PubMed]
- Gitlin, J.D. Wilson disease. Gastroenterology 2003, 125, 1868–1877. [Google Scholar] [CrossRef] [PubMed]
- Ferenci, P. Review article: Diagnosis and current therapy of Wilson’s disease. Aliment. Pharmacol. Ther. 2004, 19, 157–165. [Google Scholar] [CrossRef] [PubMed]
- Roberts, E.A.; Schilsky, M.L. Diagnosis and treatment of Wilson disease: An update. Hepatology 2008, 47, 2089–2111. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gomes, A.; Dedoussis, G.V. Geographic distribution of ATP7B mutations in Wilson disease. Ann. Hum. Biol. 2016, 43, 1–8. [Google Scholar] [CrossRef] [PubMed]
- Payne, A.S.; Kelly, E.J.; Gitlin, J.D. Functional expression of the Wilson disease protein reveals mislocalization and impaired copper-dependent trafficking of the common H1069Q mutation. Proc. Natl. Acad. Sci. USA 1998, 95, 10854–10859. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Huster, D.; Hoppert, M.; Lutsenko, S.; Zinke, J.; Lehmann, C.; Mossner, J.; Berr, F.; Caca, K. Defective cellular localization of mutant ATP7B in Wilson’s disease patients and hepatoma cell lines. Gastroenterology 2003, 124, 335–345. [Google Scholar] [CrossRef] [PubMed]
- Van den Berghe, P.V.; Stapelbroek, J.M.; Krieger, E.; de Bie, P.; van de Graaf, S.F.; de Groot, R.E.; van Beurden, E.; Spijker, E.; Houwen, R.H.; Berger, R.; et al. Reduced expression of ATP7B affected by Wilson disease-causing mutations is rescued by pharmacological folding chaperones 4-phenylbutyrate and curcumin. Hepatology 2009, 50, 1783–1795. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- D’Agostino, M.; Lemma, V.; Chesi, G.; Stornaiuolo, M.; Cannata Serio, M.; D’Ambrosio, C.; Scaloni, A.; Polishchuk, R.; Bonatti, S. The cytosolic chaperone α-crystallin B rescues folding and compartmentalization of misfolded multispan transmembrane proteins. J. Cell Sci. 2013, 126 Pt 18, 4160–4172. [Google Scholar] [CrossRef] [PubMed]
- Chesi, G.; Hegde, R.N.; Iacobacci, S.; Concilli, M.; Parashuraman, S.; Festa, B.P.; Polishchuk, E.V.; Di Tullio, G.; Carissimo, A.; Montefusco, S.; et al. Identification of p38 MAPK and JNK as new targets for correction of Wilson disease-causing ATP7B mutants. Hepatology 2016, 63, 1842–1859. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lutsenko, S.; Barnes, N.L.; Bartee, M.Y.; Dmitriev, O.Y. Function and regulation of human copper-transporting ATPases. Physiol. Rev. 2007, 87, 1011–1046. [Google Scholar] [CrossRef] [PubMed]
- La Fontaine, S.; Mercer, J.F. Trafficking of the copper-ATPases, ATP7A and ATP7B: Role in copper homeostasis. Arch. Biochem. Biophys. 2007, 463, 149–167. [Google Scholar] [CrossRef] [PubMed]
- Polishchuk, E.V.; Concilli, M.; Iacobacci, S.; Chesi, G.; Pastore, N.; Piccolo, P.; Paladino, S.; Baldantoni, D.; van IJzendoorn, S.C.; Chan, J.; et al. Wilson disease protein ATP7B utilizes lysosomal exocytosis to maintain copper homeostasis. Dev. Cell 2014, 29, 686–700. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Iida, M.; Terada, K.; Sambongi, Y.; Wakabayashi, T.; Miura, N.; Koyama, K.; Futai, M.; Sugiyama, T. Analysis of functional domains of Wilson disease protein (ATP7B) in Saccharomyces cerevisiae. FEBS Lett. 1998, 428, 281–285. [Google Scholar] [CrossRef] [Green Version]
- Kaler, S.G. ATP7A-related copper transport diseases-emerging concepts and future trends. Nat. Rev. Neurol. 2011, 7, 15–29. [Google Scholar] [CrossRef] [PubMed]
- Iorio, R.; D’Ambrosi, M.; Marcellini, M.; Barbera, C.; Maggiore, G.; Zancan, L.; Giacchino, R.; Vajro, P.; Marazzi, M.G.; Francavilla, R.; et al. Serum transaminases in children with Wilson’s disease. J. Pediatr. Gastroenterol. Nutr. 2004, 39, 331–336. [Google Scholar] [CrossRef] [PubMed]
- Beinhardt, S.; Leiss, W.; Stattermayer, A.F.; Graziadei, I.; Zoller, H.; Stauber, R.; Maieron, A.; Datz, C.; Steindl-Munda, P.; Hofer, H.; et al. Long-term outcomes of patients with Wilson disease in a large Austrian cohort. Clin. Gastroenterol. Hepatol. 2014, 12, 683–689. [Google Scholar] [CrossRef] [PubMed]
- Arrigo, A.P.; Simon, S.; Gibert, B.; Kretz-Remy, C.; Nivon, M.; Czekalla, A.; Guillet, D.; Moulin, M.; Diaz-Latoud, C.; Vicart, P. Hsp27 (HspB1) and αB-crystallin (HspB5) as therapeutic targets. FEBS Lett. 2007, 581, 3665–3674. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kannan, R.; Sreekumar, P.G.; Hinton, D.R. Novel roles for α-crystallins in retinal function and disease. Prog. Retin. Eye Res. 2012, 31, 576–604. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bhattacharyya, J.; Padmanabha Udupa, E.G.; Wang, J.; Sharma, K.K. Mini-αB-crystallin: A functional element of αB-crystallin with chaperone-like activity. Biochemistry 2006, 45, 3069–3076. [Google Scholar] [CrossRef] [PubMed]
- Nahomi, R.B.; Wang, B.; Raghavan, C.T.; Voss, O.; Doseff, A.I.; Santhoshkumar, P.; Nagaraj, R.H. Chaperone peptides of α-crystallin inhibit epithelial cell apoptosis, protein insolubilization, and opacification in experimental cataracts. J. Biol. Chem. 2013, 288, 13022–13035. [Google Scholar] [CrossRef] [PubMed]
- Sreekumar, P.G.; Chothe, P.; Sharma, K.K.; Baid, R.; Kompella, U.; Spee, C.; Kannan, N.; Manh, C.; Ryan, S.J.; Ganapathy, V.; et al. Antiapoptotic properties of α-crystallin-derived peptide chaperones and characterization of their uptake transporters in human RPE cells. Investig. Ophthalmol. Vis. Sci. 2013, 54, 2787–2798. [Google Scholar] [CrossRef] [PubMed]
- Kurnellas, M.P.; Brownell, S.E.; Su, L.; Malkovskiy, A.V.; Rajadas, J.; Dolganov, G.; Chopra, S.; Schoolnik, G.K.; Sobel, R.A.; Webster, J.; et al. Chaperone activity of small heat shock proteins underlies therapeutic efficacy in experimental autoimmune encephalomyelitis. J. Biol. Chem. 2012, 287, 36423–36434. [Google Scholar] [CrossRef] [PubMed]
- Ringe, D.; Petsko, G.A. What are pharmacological chaperones and why are they interesting? J. Biol. 2009, 8, 80. [Google Scholar] [CrossRef] [PubMed]
- Asomugha, C.O.; Gupta, R.; Srivastava, O.P. Structural and functional properties of NH(2)-terminal domain, core domain, and COOH-terminal extension of αA- and αB-crystallins. Mol. Vis. 2011, 17, 2356–2367. [Google Scholar] [PubMed]
- Gordon, G.W.; Berry, G.; Liang, X.H.; Levine, B.; Herman, B. Quantitative fluorescence resonance energy transfer measurements using fluorescence microscopy. Biophys. J. 1998, 74, 2702–2713. [Google Scholar] [CrossRef]
- Leavesley, S.J.; Rich, T.C. Overcoming limitations of FRET measurements. Cytom. A 2016, 89, 325–327. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Nahomi, R.B.; DiMauro, M.A.; Wang, B.; Nagaraj, R.H. Identification of peptides in human Hsp20 and Hsp27 that possess molecular chaperone and anti-apoptotic activities. Biochem. J. 2015, 465, 115–125. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chandhok, G.; Horvath, J.; Aggarwal, A.; Bhatt, M.; Zibert, A.; Schmidt, H.H. Functional analysis and drug response to zinc and D-penicillamine in stable ATP7B mutant hepatic cell lines. World J. Gastroenterol. 2016, 22, 4109–4119. [Google Scholar] [CrossRef] [PubMed]
- Parisi, S.; Polishchuk, E.V.; Allocca, S.; Ciano, M.; Musto, A.; Gallo, M.; Perone, L.; Ranucci, G.; Iorio, R.; Polishchuk, R.S.; et al. Characterization of the most frequent ATP7B mutation causing Wilson disease in hepatocytes from patient induced pluripotent stem cells. Sci. Rep. 2018, 8, 6247. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Buiakova, O.I.; Xu, J.; Lutsenko, S.; Zeitlin, S.; Das, K.; Das, S.; Ross, B.M.; Mekios, C.; Scheinberg, I.H.; Gilliam, T.C. Null mutation of the murine ATP7B (Wilson disease) gene results in intracellular copper accumulation and late-onset hepatic nodular transformation. Hum. Mol. Genet. 1999, 8, 1665–1671. [Google Scholar] [CrossRef] [PubMed]
- Huster, D.; Finegold, M.J.; Morgan, C.T.; Burkhead, J.L.; Nixon, R.; Vanderwerf, S.M.; Gilliam, C.T.; Lutsenko, S. Consequences of copper accumulation in the livers of the Atp7b−/− (Wilson disease gene) knockout mice. Am. J. Pathol. 2006, 168, 423–434. [Google Scholar] [CrossRef] [PubMed]
- Huster, D.; Purnat, T.D.; Burkhead, J.L.; Ralle, M.; Fiehn, O.; Stuckert, F.; Olson, N.E.; Teupser, D.; Lutsenko, S. High copper selectively alters lipid metabolism and cell cycle machinery in the mouse model of Wilson disease. J. Biol. Chem. 2007, 282, 8343–8355. [Google Scholar] [CrossRef] [PubMed]
- Polishchuk, R.; Telethon Institute of Genetics and Medicine, Pozzuoli, Italy. Personal communication, 2018.
- D’Agostino, M.; Crespi, A.; Polishchuk, E.; Generoso, S.; Martire, G.; Colombo, S.F.; Bonatti, S. ER reorganization is remarkably induced in COS-7 cells accumulating transmembrane protein receptors not competent for export from the endoplasmic reticulum. J. Membr. Biol. 2014, 247, 1149–1159. [Google Scholar] [CrossRef] [PubMed]
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Allocca, S.; Ciano, M.; Ciardulli, M.C.; D’Ambrosio, C.; Scaloni, A.; Sarnataro, D.; Caporaso, M.G.; D’Agostino, M.; Bonatti, S. An αB-Crystallin Peptide Rescues Compartmentalization and Trafficking Response to Cu Overload of ATP7B-H1069Q, the Most Frequent Cause of Wilson Disease in the Caucasian Population. Int. J. Mol. Sci. 2018, 19, 1892. https://doi.org/10.3390/ijms19071892
Allocca S, Ciano M, Ciardulli MC, D’Ambrosio C, Scaloni A, Sarnataro D, Caporaso MG, D’Agostino M, Bonatti S. An αB-Crystallin Peptide Rescues Compartmentalization and Trafficking Response to Cu Overload of ATP7B-H1069Q, the Most Frequent Cause of Wilson Disease in the Caucasian Population. International Journal of Molecular Sciences. 2018; 19(7):1892. https://doi.org/10.3390/ijms19071892
Chicago/Turabian StyleAllocca, Simona, Michela Ciano, Maria Camilla Ciardulli, Chiara D’Ambrosio, Andrea Scaloni, Daniela Sarnataro, Maria Gabriella Caporaso, Massimo D’Agostino, and Stefano Bonatti. 2018. "An αB-Crystallin Peptide Rescues Compartmentalization and Trafficking Response to Cu Overload of ATP7B-H1069Q, the Most Frequent Cause of Wilson Disease in the Caucasian Population" International Journal of Molecular Sciences 19, no. 7: 1892. https://doi.org/10.3390/ijms19071892
APA StyleAllocca, S., Ciano, M., Ciardulli, M. C., D’Ambrosio, C., Scaloni, A., Sarnataro, D., Caporaso, M. G., D’Agostino, M., & Bonatti, S. (2018). An αB-Crystallin Peptide Rescues Compartmentalization and Trafficking Response to Cu Overload of ATP7B-H1069Q, the Most Frequent Cause of Wilson Disease in the Caucasian Population. International Journal of Molecular Sciences, 19(7), 1892. https://doi.org/10.3390/ijms19071892