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Proteomic analysis of differentially expressed skin proteins in iRhom2Uncv mice

  • Liu, Bing ;
  • Xu, Yuan ;
  • Li, Wen-Long ;
  • Zeng, Lin
  • Received : 2014.01.24
  • Accepted : 2014.03.16
  • Published : 2015.01.31

Abstract

A mouse homozygous for the spontaneous mutation uncovered (Uncv) has a hairless phenotype. A 309-bp non-frameshift deletion mutation in the N-terminal cytoplasmic domain of iRhom2 was identified in Uncv mice ($iRhom2^{Uncv}$) using target region sequencing. The detailed molecular basis for how the iRhom2 mutation causes the hairless phenotype observed in the homozygous $iRhom2^{Uncv}$ mouse remains unknown. To identify differentially expressed proteins in the skin of wild-type and homozygous $iRhom2^{Uncv}$ littermates at postnatal day 5, proteomic approaches, including two-dimensional gel electrophoresis and mass spectrometry were used. Twelve proteins were differentially expressed in the skin in a comparison between wild-type and homozygous $iRhom2^{Uncv}$ mice. A selection of the proteomic results were tested and verified using qRT-PCR, western blot and immunohistochemistry. These data indicate that differentially expressed proteins, especially KRT73, MEMO1 and Coro-1, might participate in the mechanism by which iRhom2 regulates the development of murine skin.

Keywords

Hair follicle;iRhom2;Proteomic;Skin;Uncv

References

  1. Langbein L, Rogers MA, Praetzel S, Winter H and Schweizer J (2003) K6irs1, K6irs2, K6irs3, and K6irs4 represent the inner-root-sheath-specific type II epithelial keratins of the human hair follicle. J Invest Dermatol 120, 512-522 https://doi.org/10.1046/j.1523-1747.2003.12087.x
  2. Langbein L, Rogers MA, Praetzel-Wunder S, Helmke B, Schirmacher P and Schweizer J (2006) K25 (K25irs1), K26 (K25irs2), K27 (K25irs3), and K28 (K25irs4) represent the type I inner root sheath keratins of the human hair follicle. J Invest Dermatol 126, 2377-2386 https://doi.org/10.1038/sj.jid.5700494
  3. Botchkarev VA and Paus R (2003) Molecular biology of hair morphogenesis: development and cycling. J Exp Zool B Mol Dev Evol 298, 164-180 https://doi.org/10.1002/jez.b.33
  4. Langbein L and Schweizer J (2005) Keratins of the human hair follicle. Int Rev Cytol 243, 1-78 https://doi.org/10.1016/S0074-7696(05)43001-6
  5. Pieters J, Muller P and Jayachandran R (2013) On guard: coronin proteins in innate and adaptive immunity. Nat Rev Immunol 13, 510-518 https://doi.org/10.1038/nri3465
  6. Porter RM, Corden LD, Lunny DP, Smith FJ, Lane EB and McLean WH (2001) Keratin K6irs is specific to the inner root sheath of hair follicles in mice and humans. Br J Dermatol 145, 558-568 https://doi.org/10.1046/j.1365-2133.2001.04463.x
  7. Marone R, Hess D, Dankort D, Muller WJ, Hynes NE and Badache A (2004) Memo mediates ErbB2-driven cell motility. Nat Cell Biol 6, 515-522 https://doi.org/10.1038/ncb1134
  8. Sorokin AV and Chen J (2013) MEMO1, a new IRS1-interacting protein, induces epithelial-mesenchymal transition in mammary epithelial cells. Oncogene 32, 3130-3138 https://doi.org/10.1038/onc.2012.327
  9. Haenzi B, Bonny O, Masson R et al (2013) Loss of Memo, a novel FGFR regulator, results in reduced lifespan. FASEB J 28, 327-336 https://doi.org/10.1096/fj.13-228320
  10. Cui JW, Wang J, He K et al (2005) Two-dimensional electrophoresis protein profiling as an analytical tool for human acute leukemia classification. Electrophoresis 26, 268-279 https://doi.org/10.1002/elps.200406124
  11. Legue E, Sequeira I and Nicolas JF (2010) Hair follicle renewal: authentic morphogenesis that depends on a complex progression of stem cell lineages. Development 137, 569-577 https://doi.org/10.1242/dev.044123
  12. Alonso L and Fuchs E (2006) The hair cycle. J Cell Sci 119, 391-393 https://doi.org/10.1242/jcs02793
  13. Nagarajan P, Romano RA and Sinha S (2008) Transcriptional control of the differentiation program of interfollicular epidermal keratinocytes. Crit Rev Eukaryot Gene Expr 18, 57-79 https://doi.org/10.1615/CritRevEukarGeneExpr.v18.i1.50
  14. Nakamura M, Schneider MR, Schmidt-Ullrich R and Paus R (2013) Mutant laboratory mice with abnormalities in hair follicle morphogenesis, cycling, and/or structure: an update. J Dermatol Sci 69, 6-29 https://doi.org/10.1016/j.jdermsci.2012.10.001
  15. Etheridge SL, Brooke MA, Kelsell DP and Blaydon DC (2013) Rhomboid proteins: a role in keratinocyte proliferation and cancer. Cell Tissue Res 351, 301-307 https://doi.org/10.1007/s00441-012-1542-1
  16. Adrain C, Zettl M, Christova Y, Taylor N and Freeman M (2012) Tumor necrosis factor signaling requires iRhom2 to promote trafficking and activation of TACE. Science 335, 225-228 https://doi.org/10.1126/science.1214400
  17. McIlwain DR, Lang PA, Maretzky T et al (2012) iRhom2 regulation of TACE controls TNF-mediated protection against Listeria and responses to LPS. Science 335, 229-232 https://doi.org/10.1126/science.1214448
  18. Zettl M, Adrain C, Strisovsky K, Lastun V and Freeman M (2011) Rhomboid family pseudoproteases use the ER quality control machinery to regulate intercellular signaling. Cell 145, 79-91 https://doi.org/10.1016/j.cell.2011.02.047
  19. Maretzky T, McIlwain DR, Issuree PD et al (2013) iRhom2 controls the substrate selectivity of stimulated ADAM17-dependent ectodomain shedding. Proc Natl Acad Sci U S A 110, 11433-11438 https://doi.org/10.1073/pnas.1302553110
  20. Blaydon DC, Etheridge SL, Risk JM et al (2012) RHBDF2 mutations are associated with tylosis, a familial esophageal cancer syndrome. Am J Hum Genet 90, 340-346 https://doi.org/10.1016/j.ajhg.2011.12.008
  21. Li SR, Wang DP, Yu XL et al (1999) Uncv (uncovered): a new mutation causing hairloss on mouse chromosome 11. Genet Res 73, 233-238 https://doi.org/10.1017/S0016672399003808
  22. Shi YZ, Wang DP, Hu LD et al (2003) A high-resolution genetic and physical map of a mouse coat abnormality locus (Uncv). Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao (Shanghai) 35, 397-402
  23. Fuchs E (2007) Scratching the surface of skin development. Nature 445, 834-842 https://doi.org/10.1038/nature05659

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Acknowledgement

Supported by : National Natural Science Foundation of China