KIF7 Controls the Proliferation of Cells of the Respiratory Airway through Distinct Microtubule Dependent Mechanisms

English version České info

Respiratory diseases such as lung cancer, COPD, and asthma are the second leading cause of death in the United States. These diseases are heterogeneous and arise from genetic factors, environmental hazards, or developmental abnormalities that persist throughout life. An increased understanding of the genes and cellular mechanisms regulating respiratory system homeostasis and regeneration should provide information for the development of future therapeutics. We show that the gene Kif7 regulates cell proliferation, cellular density, and intracellular signaling within the epithelial and mesenchymal cells of the respiratory airway. We expand on the known role for Kif7 in regulating microtubule architecture within ciliated cells by showing that this protein regulates cell signaling in non-ciliated secretory cells. Furthermore, we show that microtubules function to regulate the abundance and activity of several factors known to be required for proper cell cycle timing. We propose that Kif7 and microtubule dynamics hone cellular signaling necessary for control of the balance between cell proliferation and cell cycle exit, and we provide evidence that Kif7 has a critical role in the maintenance of the respiratory system in postnatal life.

Vyšlo v časopise: KIF7 Controls the Proliferation of Cells of the Respiratory Airway through Distinct Microtubule Dependent Mechanisms. PLoS Genet 11(10): e32767. doi:10.1371/journal.pgen.1005525
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005525

Souhrn

Zdroje

1. Tuder RM, Yoshida T, Arap W, Pasqualini R, and Petrache I. Cellular and molecular mechanisms of alveolar destruction in emphysema an evolutionary perspective. Proc Am Thorac Soc. 2006; 3: 503–510. 16921129

2. Li H. The alveolar epithelium and pulmonary fibrosis. J Epithel Biol Pharmacol. 2009; 2: 30–35.

3. Rock JR, Hogan BL. Epithelial progenitor cells in lung development, maintenance, repair, and disease. Annu Rev Cell Dev Biol. 2011; 27: 493–512. doi: 10.1146/annurev-cellbio-100109-104040 21639799

4. Barkauskas CE, Cronce MJ, Rackley CR, Bowie EJ, Keene DR, Stripp BR, et al. Type 2 alveolar cells are stem cells in adult lung. J Clin Invest. 2013; 123: 3025–3036. doi: 10.1172/JCI68782 23921127

5. Pihan GA. Centrosome dysfunction contributes to chromosome instability, chromoanagenesis, and genome reprogramming in cancer. Front Oncol. 2013; 3: 277. doi: 10.3389/fonc.2013.00277 24282781

6. Yamamoto T, Ebisuya M, Ashida F, Okamoto K, Yonehara S, Nishida E. Continuous ERK activation downregulates antiproliferative genes throughout G1 phase to allow cell-cycle progression. Curr Biol. 2006; 16: 1171–1182. 16782007

7. Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009; 9: 153–167. doi: 10.1038/nrc2602 19238148

8. Okuda M. The role of nucleophosmin in centrosome duplication. Oncogene. 2002; 40: 6170–6174.

9. Okuda M, Horn HF, Tarapore P, Tokuyama Y, Smulian AG, Chan PK, et al. Nucleophosmin/B23 is a target of CDK2/cyclin E in centrosome duplication. Cell. 2000; 103: 127–140. 11051553

10. Jiang J, Hui C. Hedgehog signaling in development and cancer. Dev Cell. 2008; 15: 801–812. doi: 10.1016/j.devcel.2008.11.010 19081070

11. He M, Subramanian R, Bangs F, Omelchenko O, Liem KF, Kapoor TM, et al. The kinesin-4 protein Kif7 regulates mammalian hedgehog signaling by organizing the cilium tip compartment. Nat Cell Biol. 2014; 16: 663–672. doi: 10.1038/ncb2988 24952464

12. Schneider L, Clement CA, Teilmann SC, Pazour GJ, Hoffmann EK, Satir P, et al. PDGFRalphaalpha signaling is regulated through the primary cilium in fibroblasts. Curr Biol. 2005; 15: 1861–1866. 16243034

13. Ezratty EJ, Stokes N, Chai S, Shah AS, Williams SE, Fuchs E. A role for the primary cilium in notch signaling and epidermal differentiation during skin development. Cell. 2011; 145: 1129–1141. doi: 10.1016/j.cell.2011.05.030 21703454

14. Coles GL, Ackerman KG. Kif7 is required for the patterning and differentiation of the diaphragm in a model of syndromic congenital diaphragmatic hernia. Proc Natl Acad Sci U S A. 2013; 110: E1898–1905. doi: 10.1073/pnas.1222797110 23650387

15. Locker M, Agathocleous M, Amato MA, Parain K, Harris WA, Perron M. Hedgehog signaling and the retina: insights into the mechanisms controlling the proliferative properties of neural precursors. Genes Dev. 2006; 21: 3036–3048.

16. Dafinger C, Liebau MC, Elsayed SM, Hellenbroich Y, Boltshauser E, Korenk GC, et al. Mutations in KIF7 link Joubert syndrome with sonic hedgehog signaling and microtubule dynamics. J Clin Invest. 2011; 121: 2662–2667. doi: 10.1172/JCI43639 21633164

17. Tariki M, Dhanyamraju PK, Fendrich V, Borggrefe T, Feldmann G, Lauth M. The Yes-associated protein controls the cell density regulation of hedgehog signaling. Oncogenesis. 2014; 11;3: e112. doi: 10.1038/oncsis.2014.27 25111861

18. Resnitzky D, Gossen M, Bujard H, Reed SI. Acceleration of the G1/S phase transition by expression of cyclins D1 and E with an inducible system. Mol Cell Biol. 1994; 14:1669–1679. 8114703

19. Piperno G, Fuller MT. Monoclonal antibodies specific for an acetylated form of alpha-tubulin recognize the antigen in cilia and flagella from a variety of organisms. J Cell Biol. 1985; 101:2085–94. 2415535

20. Kusakabe T, Maeda M, Hoshi N, Sugino T, Watanabe K, Takeaki F, et al. Fatty acid synthase is expressed mainly in adult hormone-sensitive cells or cells with high lipid metabolism and in proliferating fetal cells. J Histochem Cytochem. 2000; 48: 613–622. 10769045

21. Lindahl P, Karlsson L, Hellstrom M, Gebre-Medhin S, Willetts K, Heath JK, et al. Alveogenesis failure in PDGFA-deficient mice is coupled to lack of distal spreading of alveolar smooth muscle cell progenitors during lung development. Development. 1997; 124: 3943–3953. 9374392

22. Varisco BM, Ambalavanan N, Whitsett JA, Hagood JS. Thy-1 signals through PPARγ to promote lipofibroblast differentiation in the developing lung. Am J Respir Cell Mol Biol. 2012; 46: 765–772. doi: 10.1165/rcmb.2011-0316OC 22268140

23. Bellusci S, Furuta Y, Rush MG, Henderson R, Winnier G, Hogan BL. Involvement of Sonic hedgehog (Shh) in mouse embryonic lung growth and morphogenesis. Development. 1997; 124, 53–63. 9006067

24. Liu L, Kugler MC, Loomis CA, Samdani R, Zhao Z, Chen GJ, et al. Hedgehog signaling in neonatal and adult lung. Am J Respir Cell Mol Biol. 2013; 48:703–710. doi: 10.1165/rcmb.2012-0347OC 23371063

25. Duman-Scheel M, Weng L, Xin S, Du W. Hedgehog regulates cell growth and proliferation by inducing Cyclin D and Cyclin E. Nature. 2002; 417: 299–304. 12015606

26. Rao SS, Kohtz DS. Positive and negative regulation of D-type cyclin expression in skeletal myoblasts by basic fibroblast growth factor and transforming growth factor beta. A role for cyclin D1 in control of myoblast differentiation. J Biol Chem. 1995; 270: 4093–4100. 7876159

27. Skapek SX, Lin SC, Jablonski MM, McKeller RN, Tan M, Hu N, et al. Persistent expression of cyclin D1 disrupts normal photoreceptor differentiation and retina development. Oncogene. 2001; 20: 6742–6751. 11709709

28. Gelfand VI, Bershadsky AD. Microtubule dynamics: mechanism, regulation, and function. Annu. Rev. Cell Bio. 1991; 7: 93–116.

29. Kimura H, Stephen D, Joyner A, Curran T. Gli1 is important for medulloblastoma formation in Ptc1+/- mice. Oncogene. 2005; 24: 4026–4036. 15806168

30. Desai TJ, Brownfield DG, Krasnow MA. Alveolar progenitor and stem cells in lung development, renewal and cancer. Nature. 2014; 507: 190–194. doi: 10.1038/nature12930 24499815

31. Reznikoff CA, Brankow DW, Heidelberger C. Establishment and Characterization of a Cloned Line of C3H Mouse Embryo Cells Sensitive to Postconfluence Inhibition of Division. Cancer Res. 1973; 33, 3231–3238. 4357355

32. O'Rourke BP, Gomez-Ferreria MA, Berk RH, Hackl AM, Nicholas MP, et al. Cep192 controls the balance of centrosome and non-centrosomal microtubules during interphase. PLoS One. 2014; 9: e101001. doi: 10.1371/journal.pone.0101001 24971877

33. Alexander GS, Ritchie BC, Maloney JE. Scanning electron microscopy of pulmonary alveolar capillary vessels. Thorax. 1973; 28: 222–227. 4731118

34. Fang X, Song Y, Hirsch J, Galietta LJ, Pedemonte N, Zemans RL, et al. Contribution of CFTR to apical-basolateral fluid transport in cultured human alveolar epithelial type II cells. Am J Physiol Lung Cell Mol Physiol. 2006; 290: 242–249.

35. Wikenheiser KA, Vorbroker DK, Rice WR, Clark JC, Bachurski CJ, Oie HK, et al. Production of immortalized distal respiratory epithelial cell lines from surfactant protein C/simian virus 40 large tumor antigen transgenic mice. Proc. Natl. Acad. Sci. USA. 1993; 90: 11029–11033. 8248207

36. Chen JK, Taipale J, Young KE, Maiti T, Beachy PA. Small molecule modulation of Smoothened activity. Proc Natl Acad Sci U S A. 2002; 99,14071–14076. 12391318

37. Hendzel MJ, Wei Y, Mancini MA, Van Hooser A, Ranalli T, Brinkley BR, et al. Mitosis-specific phosphorylation of histone H3 initiates primarily within pericentromeric heterochromatin during G2 and spreads in an ordered fashion coincident with mitotic chromosome condensation. Chromosoma. 1997; 106: 348–360. 9362543

38. Zeng X, Sigoillot F, Gaur S, Choi S, Pfaff KL, Oh DC, et al. Pharmacologic inhibition of the anaphase-promoting complex induces a spindle checkpoint-dependent mitotic arrest in the absence of spindle damage. Cancer Cell. 2010; 18: 382–395. doi: 10.1016/j.ccr.2010.08.010 20951947

39. Jackman M, Lindon C, Nigg EA, Pines J. Active cyclin B1-Cdk1 first appears on centrosomes in prophase. Nat Cell Biol. 2003; 5:143–148. 12524548

40. Mantel C, Braun SE, Reid S, Henegariu O, Liu L, Hangoc G, et al. p21cip-1/waf-1 deficiency causes deformed nuclear architecture, centriole overduplication, polyploidy, and relaxed microtubule damage checkpoints in human hematopoietic cells. Blood. 1999; 93: 1390–1398. 9949183

41. Lacey KR, Jackson PK, Stearns T. Cyclin-dependent kinase control of centrosome duplication. Proc Natl Acad Sci USA. 1999; 96: 2817–2822. 10077594

42. Hu D, Qiao X, Wu G, Wan Y. The emerging role of APC/CCdh1 in development. Semin Cell Dev Biol. 2011; 22: 579–585. doi: 10.1016/j.semcdb.2011.03.012 21497201

43. Kraft C, Herzog F, Gieffers C, Mechtler K, Hagting A, Pines J, et al. Mitotic regulation of the human anaphase‐promoting complex by phosphorylation. EMBO J. 2003; 22: 6598–6609. 14657031

44. García-Higuera I, Manchado E, Dubus P, Cañamero M, Méndez J, Moreno S, et al. Genomic stability and tumour suppression by the APC/C cofactor Cdh1. Nat Cell Biol. 2008; 10: 802–811. doi: 10.1038/ncb1742 18552834

45. Song L, Craney A, Rape M. Microtubule-dependent regulation of mitotic protein degradation. Mol Cell. 2014; 5: 179–192

46. Manning BD, and Cantley LC. AKT/PKB signaling: navigating downstream. Cell 2007; 129: 1261–1274. 17604717

47. Trielli MO, Andreassen PR, Lacroix FB, Margolis RL. Differential taxol-dependent arrest of transformed and nontransformed cells in the G1 phase of the cell cycle, and specific-related mortality of transformed cells. J Cell Biol. 1996; 135:689–700. 8909543

48. Mantel CR, Braun SE, Lee Y, Kim YJ, Broxmeyer HE. The interphase microtubule damage checkpoint defines an S-phase commitment point and does not require p21(waf-1). Blood. 2001; 97: 1505–1507. 11222400

49. Uetake Y, Sluder G. An intact microtubule cytoskeleton is not needed for cell cycle progression if the preceding mitosis is of normal duration. Curr Biol. 2007; 17: 2081–2086. 18060787

50. Giannakakou P, Nakano M, Nicolaou KC, O’Brate A, Yu J, Blagosklonny MV, et al. Enhanced microtubule-dependent trafficking and p53 nuclear accumulation by suppression of microtubule dynamics. Proc Natl Acad Sci USA. 2002; 99: 10855–10860. 12145320

51. Rovinaa D, Fontanaa L, Montia L, Noviellia C, Paninib N, Sirchia S, et al. Microtubule-associated protein/microtubule affinity-regulating kinase 4 (MARK4) plays a role in cell cycle progression and cytoskeletal dynamics. Eur J Cell Biol. 2014; 93: 355–365. doi: 10.1016/j.ejcb.2014.07.004 25123532

52. Aguilar A, Becker L, Tedeschi T, Heller S, Iomini C, Nachury M.Α-tubulin K40 acetylation is required for contact inhibition of proliferation and cell-substrate adhesion. Mol Biol Cell. 2014; 25,1854–1866. doi: 10.1091/mbc.E13-10-0609 24743598

53. Osborn L, Kunkel S, Nabel GJ. Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc Natl Acad Sci USA. 1989; 86: 2336–2340. 2494664