Calpain-5 Mutations Cause Autoimmune Uveitis, Retinal Neovascularization, and Photoreceptor Degeneration

English version České info

Autosomal dominant neovascular inflammatory vitreoretinopathy (ADNIV) is an autoimmune condition of the eye that sequentially mimics uveitis, retinitis pigmentosa, and proliferative diabetic retinopathy as it progresses to complete blindness. We identified two different missense mutations in the CAPN5 gene in three ADNIV kindreds. CAPN5 encodes calpain-5, a calcium-activated cysteine protease that is expressed in retinal photoreceptor cells. Both mutations cause mislocalization from the cell membrane to the cytosol, and structural modeling reveals that both mutations lie within a calcium-sensitive domain near the active site. CAPN5 is only the second member of the large calpain gene family to cause a human Mendelian disorder, and this is the first report of a specific molecular cause for autoimmune eye disease. Further investigation of these mutations is likely to provide insight into the pathophysiologic mechanisms of common diseases ranging from autoimmune disorders to diabetic retinopathy.

Vyšlo v časopise: Calpain-5 Mutations Cause Autoimmune Uveitis, Retinal Neovascularization, and Photoreceptor Degeneration. PLoS Genet 8(10): e32767. doi:10.1371/journal.pgen.1003001
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1003001

Souhrn

Zdroje

1. BennettSR, FolkJC, KimuraAE, RussellSR, StoneEM, et al. (1990) Autosomal dominant neovascular inflammatory vitreoretinopathy. Ophthalmology 97 : 1125–1135; discussion 1135–1126.

2. MahajanVB, FolkJC, FingertJH, SkeieJM, KinnickTR, ScheetzTC, BassukAG, BJRM, SheffieldVC, StoneEM (2011) Genetic Analysis and Phenotypic Staging of Autosomal Dominant Neovascular Inflammatory Vitreoretinopathy. ARVO May 01 : 62/A175.

3. PascoliniD, MariottiSP (2012) Global estimates of visual impairment: 2010. Br J Ophthalmol 96 : 614–618.

4. ResnikoffS, PascoliniD, Etya'aleD, KocurI, PararajasegaramR, et al. (2004) Global data on visual impairment in the year 2002. Bull World Health Organ 82 : 844–851.

5. SheffieldVC, StoneEM (2011) Genomics and the eye. N Engl J Med 364 : 1932–1942.

6. BergerW, Kloeckener-GruissemB, NeidhardtJ (2010) The molecular basis of human retinal and vitreoretinal diseases. Prog Retin Eye Res 29 : 335–375.

7. CaspiRR (2010) A look at autoimmunity and inflammation in the eye. J Clin Invest 120 : 3073–3083.

8. FrankRN (2004) Diabetic retinopathy. N Engl J Med 350 : 48–58.

9. PastorJC, de la RuaER, MartinF (2002) Proliferative vitreoretinopathy: risk factors and pathobiology. Prog Retin Eye Res 21 : 127–144.

10. StoneEM, KimuraAE, FolkJC, BennettSR, NicholsBE, et al. (1992) Genetic linkage of autosomal dominant neovascular inflammatory vitreoretinopathy to chromosome 11q13. Hum Mol Genet 1 : 685–689.

11. DearN, MatenaK, VingronM, BoehmT (1997) A new subfamily of vertebrate calpains lacking a calmodulin-like domain: implications for calpain regulation and evolution. Genomics 45 : 175–184.

12. HannaRA, CampbellRL, DaviesPL (2008) Calcium-bound structure of calpain and its mechanism of inhibition by calpastatin. Nature 456 : 409–412.

13. MoldoveanuT, GehringK, GreenDR (2008) Concerted multi-pronged attack by calpastatin to occlude the catalytic cleft of heterodimeric calpains. Nature 456 : 404–408.

14. MoldoveanuT, HosfieldCM, LimD, ElceJS, JiaZ, et al. (2002) A Ca(2+) switch aligns the active site of calpain. Cell 108 : 649–660.

15. LeloupL, ShaoH, BaeYH, DeasyB, StolzD, et al. (2010) m-Calpain activation is regulated by its membrane localization and by its binding to phosphatidylinositol 4,5-bisphosphate. J Biol Chem 285 : 33549–33566.

16. MichettiM, SalaminoF, TedescoI, AvernaM, MinafraR, et al. (1996) Autolysis of human erythrocyte calpain produces two active enzyme forms with different cell localization. FEBS Lett 392 : 11–15.

17. ZatzM, StarlingA (2005) Calpains and disease. N Engl J Med 352 : 2413–2423.

18. ErmolovaN, KudryashovaE, DiFrancoM, VergaraJ, KramerovaI, et al. (2011) Pathogenity of some limb girdle muscular dystrophy mutations can result from reduced anchorage to myofibrils and altered stability of calpain 3. Hum Mol Genet 20 : 3331–3345.

19. CroallDE, DeMartinoGN (1991) Calcium-activated neutral protease (calpain) system: structure, function, and regulation. Physiol Rev 71 : 813–847.

20. GollDE, ThompsonVF, LiH, WeiW, CongJ (2003) The calpain system. Physiol Rev 83 : 731–801.

21. KawasakiH, KawashimaS (1996) Regulation of the calpain-calpastatin system by membranes (review). Mol Membr Biol 13 : 217–224.

22. DuVerleDA, OnoY, SorimachiH, MamitsukaH (2011) Calpain cleavage prediction using multiple kernel learning. PLoS ONE 6: e19035 doi:10.1371/journal.pone.0019035

23. WaghrayA, WangDS, McKinseyD, HayesRL, WangKK (2004) Molecular cloning and characterization of rat and human calpain-5. Biochem Biophys Res Commun 324 : 46–51.

24. BarnesTM, HodgkinJ (1996) The tra-3 sex determination gene of Caenorhabditis elegans encodes a member of the calpain regulatory protease family. EMBO J 15 : 4477–4484.

25. DearTN, BoehmT (1999) Diverse mRNA expression patterns of the mouse calpain genes Capn5, Capn6 and Capn11 during development. Mech Dev 89 : 201–209.

26. HuangY, WangKK (2001) The calpain family and human disease. Trends Mol Med 7 : 355–362.

27. HorikawaY, OdaN, CoxNJ, LiX, Orho-MelanderM, et al. (2000) Genetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus. Nat Genet 26 : 163–175.

28. SaezME, Martinez-LarradMT, Ramirez-LorcaR, Gonzalez-SanchezJL, ZabenaC, et al. (2007) Calpain-5 gene variants are associated with diastolic blood pressure and cholesterol levels. BMC Med Genet 8 : 1.

29. RichardI, BrouxO, AllamandV, FougerousseF, ChiannilkulchaiN, et al. (1995) Mutations in the proteolytic enzyme calpain 3 cause limb-girdle muscular dystrophy type 2A. Cell 81 : 27–40.

30. MarcilhacA, RaynaudF, ClercI, BenyaminY (2006) Detection and localization of calpain 3-like protease in a neuronal cell line: possible regulation of apoptotic cell death through degradation of nuclear IkappaBalpha. Int J Biochem Cell Biol 38 : 2128–2140.

31. KrahnM, Lopez de MunainA, StreichenbergerN, BernardR, PecheuxC, et al. (2006) CAPN3 mutations in patients with idiopathic eosinophilic myositis. Ann Neurol 59 : 905–911.

32. FranzT, WincklerL, BoehmT, DearTN (2004) Capn5 is expressed in a subset of T cells and is dispensable for development. Mol Cell Biol 24 : 1649–1654.

33. VanderklishPW, BahrBA (2000) The pathogenic activation of calpain: a marker and mediator of cellular toxicity and disease states. Int J Exp Pathol 81 : 323–339.

34. AzumaM, ShearerTR (2008) The role of calcium-activated protease calpain in experimental retinal pathology. Surv Ophthalmol 53 : 150–163.

35. TuckerBA, ScheetzTE, MullinsRF, DeLucaAP, HoffmannJM, et al. (2011) Exome sequencing and analysis of induced pluripotent stem cells identify the cilia-related gene male germ cell-associated kinase (MAK) as a cause of retinitis pigmentosa. Proc Natl Acad Sci U S A 108: E569–576.

36. TrapnellC, PachterL, SalzbergSL (2009) TopHat: discovering splice junctions with RNA-Seq. Bioinformatics 25 : 1105–1111.

37. TrapnellC, WilliamsBA, PerteaG, MortazaviA, KwanG, et al. (2010) Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation. Nat Biotechnol 28 : 511–515.