Keratin 76 Is Required for Tight Junction Function and Maintenance of the Skin Barrier
The generation of knockout mice is a central approach to studying gene function. We have examined the consequences of the germ line inactivation of Keratin 76 in mice and in doing so we reveal a previously undescribed mechanism by which keratin intermediate filaments regulate cellular interactions and tissue homeostasis. Our study supports an emerging body of evidence which challenges the classical view of the keratin intermediate filaments as simple structural proteins, highlighting Krt76 as a gene whose function is indispensable for barrier function and skin wound repair as a result of its novel interaction with tight junction complexes. This study identifies a previously unknown and critical link between intermediate filaments and tight junctions where intermediate filament dysfunction influences skin disease.
Vyšlo v časopise:
Keratin 76 Is Required for Tight Junction Function and Maintenance of the Skin Barrier. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004706
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pgen.1004706
Souhrn
The generation of knockout mice is a central approach to studying gene function. We have examined the consequences of the germ line inactivation of Keratin 76 in mice and in doing so we reveal a previously undescribed mechanism by which keratin intermediate filaments regulate cellular interactions and tissue homeostasis. Our study supports an emerging body of evidence which challenges the classical view of the keratin intermediate filaments as simple structural proteins, highlighting Krt76 as a gene whose function is indispensable for barrier function and skin wound repair as a result of its novel interaction with tight junction complexes. This study identifies a previously unknown and critical link between intermediate filaments and tight junctions where intermediate filament dysfunction influences skin disease.
Zdroje
1. FuchsE, WeberK (1994) Intermediate filaments: structure, dynamics, function, and disease. Annu Rev Biochem 63: 345–382.
2. GeislerN, WeberK (1982) The amino acid sequence of chicken muscle desmin provides a common structural model for intermediate filament proteins. EMBO J 1: 1649–1656.
3. LaneEB, McLeanWH (2004) Keratins and skin disorders. J Pathol 204: 355–366.
4. ParryDA, StrelkovSV, BurkhardP, AebiU, HerrmannH (2007) Towards a molecular description of intermediate filament structure and assembly. Exp Cell Res 313: 2204–2216.
5. FuchsE, ClevelandDW (1998) A structural scaffolding of intermediate filaments in health and disease. Science 279: 514–519.
6. OsbornM (1983) Intermediate filaments as histologic markers: an overview. J Invest Dermatol 81: 104s–109s.
7. SimpsonCL, PatelDM, GreenKJ (2011) Deconstructing the skin: cytoarchitectural determinants of epidermal morphogenesis. Nat Rev Mol Cell Biol 12: 565–580.
8. OmaryMB, KuNO, StrnadP, HanadaS (2009) Toward unraveling the complexity of simple epithelial keratins in human disease. J Clin Invest 119: 1794–1805.
9. CoulombePA, OmaryMB (2002) 'Hard' and 'soft' principles defining the structure, function and regulation of keratin intermediate filaments. Curr Opin Cell Biol 14: 110–122.
10. KuNO, ZhouX, ToivolaDM, OmaryMB (1999) The cytoskeleton of digestive epithelia in health and disease. Am J Physiol 277: G1108–1137.
11. OrioloAS, WaldFA, RamsauerVP, SalasPJ (2007) Intermediate filaments: a role in epithelial polarity. Exp Cell Res 313: 2255–2264.
12. ToivolaDM, TaoGZ, HabtezionA, LiaoJ, OmaryMB (2005) Cellular integrity plus: organelle-related and protein-targeting functions of intermediate filaments. Trends Cell Biol 15: 608–617.
13. KimS, WongP, CoulombePA (2006) A keratin cytoskeletal protein regulates protein synthesis and epithelial cell growth. Nature 441: 362–365.
14. XuJ, MarzettiE, SeoAY, KimJS, ProllaTA, et al. (2010) The emerging role of iron dyshomeostasis in the mitochondrial decay of aging. Mech Ageing Dev 131: 487–493.
15. KimS, CoulombePA (2010) Emerging role for the cytoskeleton as an organizer and regulator of translation. Nat Rev Mol Cell Biol 11: 75–81.
16. NiessenCM (2007) Tight junctions/adherens junctions: basic structure and function. J Invest Dermatol 127: 2525–2532.
17. FuruseM, HataM, FuruseK, YoshidaY, HaratakeA, et al. (2002) Claudin-based tight junctions are crucial for the mammalian epidermal barrier: a lesson from claudin-1-deficient mice. J Cell Biol 156: 1099–1111.
18. KirschnerN, BohnerC, RachowS, BrandnerJM (2010) Tight junctions: is there a role in dermatology? Arch Dermatol Res 302: 483–493.
19. De BenedettoA, RafaelsNM, McGirtLY, IvanovAI, GeorasSN, et al. (2011) Tight junction defects in patients with atopic dermatitis. J Allergy Clin Immunol 127: 773–786–e771–777.
20. KirschnerN, PoetzlC, von den DrieschP, WladykowskiE, MollI, et al. (2009) Alteration of tight junction proteins is an early event in psoriasis: putative involvement of proinflammatory cytokines. Am J Pathol 175: 1095–1106.
21. FanningAS, JamesonBJ, JesaitisLA, AndersonJM (1998) The tight junction protein ZO-1 establishes a link between the transmembrane protein occludin and the actin cytoskeleton. J Biol Chem 273: 29745–29753.
22. WhiteJK, GerdinAK, KarpNA, RyderE, BuljanM, et al. (2013) Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes. Cell 154: 452–464.
23. DiTommaso T, Jones L, Cottle DL, Program. TWMG, Gerdin A-K, et al. (2014) Identification of genes important for cutaneous function revealed by a large scale reverse genetic screen in the mouse. PLoS Gen, DOI: 101371/journalpgen1004705
24. SkarnesWC, RosenB, WestAP, KoutsourakisM, BushellW, et al. (2011) A conditional knockout resource for the genome-wide study of mouse gene function. Nature 474: 337–342.
25. CollinC, OuhayounJP, GrundC, FrankeWW (1992) Suprabasal marker proteins distinguishing keratinizing squamous epithelia: cytokeratin 2 polypeptides of oral masticatory epithelium and epidermis are different. Differentiation 51: 137–148.
26. Liakath-AliK, VancollieVE, HeathE, SmedleyDP, EstabelJ, et al. (2014) Novel skin phenotypes revealed by a genome-wide mouse reverse genetic screen. Nat Commun 5: 3540.
27. PaladiniRD, TakahashiK, BravoNS, CoulombePA (1996) Onset of re-epithelialization after skin injury correlates with a reorganization of keratin filaments in wound edge keratinocytes: defining a potential role for keratin 16. J Cell Biol 132: 381–397.
28. MadsenP, RasmussenHH, LeffersH, HonoreB, CelisJE (1992) Molecular cloning and expression of a novel keratinocyte protein (psoriasis-associated fatty acid-binding protein [PA-FABP]) that is highly up-regulated in psoriatic skin and that shares similarity to fatty acid-binding proteins. J Invest Dermatol 99: 299–305.
29. OgawaE, OwadaY, IkawaS, AdachiY, EgawaT, et al. (2011) Epidermal FABP (FABP5) regulates keratinocyte differentiation by 13(S)-HODE-mediated activation of the NF-kappaB signaling pathway. J Invest Dermatol 131: 604–612.
30. BaranW, SzepietowskiJC, Szybejko-MachajG (2005) Expression of p53 protein in psoriasis. Acta dermatovenerologica Alpina, Panonica, et Adriatica 14: 79–83.
31. de RieMA, GoedkoopAY, BosJD (2004) Overview of psoriasis. Dermatologic therapy 17: 341–349.
32. ThewesM, StadlerR, KorgeB, MischkeD (1991) Normal psoriatic epidermis expression of hyperproliferation-associated keratins. Archives of dermatological research 283: 465–471.
33. BertaMA, BakerCM, CottleDL, WattFM (2010) Dose and context dependent effects of Myc on epidermal stem cell proliferation and differentiation. EMBO Mol Med 2: 16–25.
34. CottleDL, KretzschmarK, SchweigerPJ, QuistSR, GollnickHP, et al. (2013) c-MYC-Induced Sebaceous Gland Differentiation Is Controlled by an Androgen Receptor/p53 Axis. Cell reports 3: 427–441.
35. LinJY, FisherDE (2007) Melanocyte biology and skin pigmentation. Nature 445: 843–850.
36. FrenchAD, FioriJL, CamilliTC, LeotlelaPD, O'ConnellMP, et al. (2009) PKC and PKA phosphorylation affect the subcellular localization of claudin-1 in melanoma cells. Int J Med Sci 6: 93–101.
37. SjoA, MagnussonKE, PetersonKH (2010) Protein kinase C activation has distinct effects on the localization, phosphorylation and detergent solubility of the claudin protein family in tight and leaky epithelial cells. J Membr Biol 236: 181–189.
38. MrsnyRJ, BrownGT, Gerner-SmidtK, BuretAG, MeddingsJB, et al. (2008) A key claudin extracellular loop domain is critical for epithelial barrier integrity. Am J Pathol 172: 905–915.
39. ArabzadehA, TroyTC, TurksenK (2007) Changes in the distribution pattern of Claudin tight junction proteins during the progression of mouse skin tumorigenesis. BMC cancer 7: 196.
40. WatsonRE, PoddarR, WalkerJM, McGuillI, HoareLM, et al. (2007) Altered claudin expression is a feature of chronic plaque psoriasis. J Pathol 212: 450–458.
41. DhawanP, SinghAB, DeaneNG, NoY, ShiouSR, et al. (2005) Claudin-1 regulates cellular transformation and metastatic behavior in colon cancer. J Clin Invest 115: 1765–1776.
42. HoughCD, Sherman-BaustCA, PizerES, MontzFJ, ImDD, et al. (2000) Large-scale serial analysis of gene expression reveals genes differentially expressed in ovarian cancer. Cancer Res 60: 6281–6287.
43. AmbatipudiS, BhosalePG, HeathE, PandeyM, KumarG, et al. (2013) Downregulation of keratin 76 expression during oral carcinogenesis of human, hamster and mouse. PloS one 8: e70688.
44. FarleyFW, SorianoP, SteffenLS, DymeckiSM (2000) Widespread recombinase expression using FLPeR (flipper) mice. Genesis 28: 106–110.
45. VasioukhinV, DegensteinL, WiseB, FuchsE (1999) The magical touch: genome targeting in epidermal stem cells induced by tamoxifen application to mouse skin. Proc Natl Acad Sci U S A 96: 8551–8556.
46. SchwenkF, BaronU, RajewskyK (1995) A cre-transgenic mouse strain for the ubiquitous deletion of loxP-flanked gene segments including deletion in germ cells. Nucleic Acids Res 23: 5080–5081.
47. Adams N, Gale N (2006) High Resolution Gene Expression Analysis in Mice Using Genetically Inserted Reporter Genes. In: Pease S, Lois C, editors. Mammalian and Avian Transgenesis — New Approaches: Springer Berlin Heidelberg. pp. 131–172.
48. SchindelinJ, Arganda-CarrerasI, FriseE, KaynigV, LongairM, et al. (2012) Fiji: an open-source platform for biological-image analysis. Nat Methods 9: 676–682.
49. LichtiU, AndersJ, YuspaSH (2008) Isolation and short-term culture of primary keratinocytes, hair follicle populations and dermal cells from newborn mice and keratinocytes from adult mice for in vitro analysis and for grafting to immunodeficient mice. Nat Protoc 3: 799–810.
50. ChenY, MerzdorfC, PaulDL, GoodenoughDA (1997) COOH terminus of occludin is required for tight junction barrier function in early Xenopus embryos. J Cell Biol 138: 891–899.
51. WiradjajaF, CottleDL, JonesL, SmythI (2013) Regulation of PDGFC signalling and extracellular matrix composition by FREM1 in mice. Dis Model Mech 6: 1426–1433.
52. SmythI, HackingDF, HiltonAA, MukhamedovaN, MeiklePJ, et al. (2008) A mouse model of harlequin ichthyosis delineates a key role for Abca12 in lipid homeostasis. PLoS Genet 4: e1000192.
Štítky
Genetika Reprodukčná medicínaČlánok vyšiel v časopise
PLOS Genetics
2014 Číslo 10
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