リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

リケラボ 全国の大学リポジトリにある学位論文・教授論文を一括検索するならリケラボ論文検索大学・研究所にある論文を検索できる

大学・研究所にある論文を検索できる 「Bex1 is essential for ciliogenesis and harbours biomolecular condensate-forming capacity.」の論文概要。リケラボ論文検索は、全国の大学リポジトリにある学位論文・教授論文を一括検索できる論文検索サービスです。

コピーが完了しました

URLをコピーしました

論文の公開元へ論文の公開元へ
書き出し

Bex1 is essential for ciliogenesis and harbours biomolecular condensate-forming capacity.

HIBINO Emi 00803371 0000-0002-0846-8842 ICHIYAMA Yusuke 10749021 0000-0002-9134-9886 TSUKAMURA Atsushi SENJU Yosuke MORIMUNE Takao OHJI Masahito 90252650 MARUO Yoshihiro 80314160 NISHIMURA Masaki 40322739 MORI Masaki 10602625 0000-0001-7632-3875 滋賀医科大学

2022.02.10

概要

Background:
Primary cilia are sensory organelles crucial for organ development. The pivotal structure of the primary cilia is a microtubule that is generated via tubulin polymerization reaction that occurs in the basal body. It remains to be elucidated how molecules with distinct physicochemical properties contribute to the formation of the primary cilia.

Results:
Here we show that brain expressed X-linked 1 (Bex1) plays an essential role in tubulin polymerization and primary cilia formation. The Bex1 protein shows the physicochemical property of being an intrinsically disordered protein (IDP). Bex1 shows cell density-dependent accumulation as a condensate either in nucleoli at a low cell density or at the apical cell surface at a high cell density. The apical Bex1 localizes to the basal body. Bex1 knockout mice present ciliopathy phenotypes and exhibit ciliary defects in the retina and striatum. Bex1 recombinant protein shows binding capacity to guanosine triphosphate (GTP) and forms the condensate that facilitates tubulin polymerization in the reconstituted system.

Conclusions:
Our data reveals that Bex1 plays an essential role for the primary cilia formation through providing the reaction field for the tubulin polymerization.

この論文で使われている画像

参考文献

1. Jam FA, Kadota Y, Mendsaikhan A, Tooyama I, Mori M. Identification of juvenility-associated genes in the mouse hepatocytes and cardiomyo- cytes. Sci Rep. 2018;8:3132. https://doi.org/10.1038/s41598-018-21445-3.

2. Yang Y, Tetti M, Vohra T, Adolf C, Seissler J, Hristov M, et al. BEX1 Is Differen- tially Expressed in Aldosterone-Producing Adenomas and Protects Human Adrenocortical Cells from Ferroptosis. Hypertension. 2021; May:1647–58.

3. Wang Q, Liang N, Yang T, Li Y, Li J, Huang Q, et al. DNMT1-mediated meth- ylation of BEX1 regulates stemness and tumorigenicity in liver cancer. J Hepatol. 2021;75:1142–53. https://doi.org/10.1016/j.jhep.2021.06.025.

4. Doi T, Ogawa H, Tanaka Y, Hayashi Y, Maniwa Y. <em>Bex1</em> sig- nificantly contributes to the proliferation and invasiveness of malignant tumor cells. Oncol Lett. 2020;20:1–1. https://doi.org/10.3892/ol.2020. 12226.

5. Koo JH, Smiley MA, Lovering RM, Margolis FL. Bex1 knock out mice show altered skeletal muscle regeneration. Biochem Biophys Res Commun. 2007;363:405–10.

6. Accornero F, Schips TG, Petrosino JM, Gu S-Q, Kanisicak O, van Berlo JH, et al. BEX1 is an RNA-dependent mediator of cardiomyopathy. Nat Com- mun. 2017;8:1875. https://doi.org/10.1038/s41467-017-02005-1.

7. Nonaka S, Tanaka Y, Okada Y, Takeda S, Harada A, Kanai Y, et al. Randomi- zation of Left–Right Asymmetry due to Loss of Nodal Cilia Generating Leftward Flow of Extraembryonic Fluid in Mice Lacking KIF3B Motor Protein. Cell. 1998;95:829–37. https://doi.org/10.1016/S0092-8674(00) 81705-5.

8. Sawamoto K. New Neurons Follow the Flow of Cerebrospinal Fluid in the Adult Brain. Science. 2006;311:629–32. https://doi.org/10.1126/science. 1119133.

9. Mirzadeh Z, Kusne Y, Duran-Moreno M, Cabrales E, Gil-Perotin S, Ortiz C, et al. Bi- and uniciliated ependymal cells define continuous floor-plate- derived tanycytic territories. Nat Commun. 2017;8:1–12. https://doi.org/ 10.1038/ncomms13759.

10. Oh EC, Katsanis N. Cilia in vertebrate development and disease. Develop- ment. 2012;139:443–8. https://doi.org/10.1242/dev.050054.

11. Malicki JJ, Johnson CA. The Cilium: Cellular Antenna and Central Process- ing Unit. Trends Cell Biol. 2017;27:126–40. https://doi.org/10.1016/j.tcb. 2016.08.002.

12. Singla V, Reiter JF. The primary cilium as the cell’s antenna: Signaling at a sensory organelle. Science. 2006;313:629–33.

13. Berbari NF, O’Connor AK, Haycraft CJ, Yoder BK. The Primary Cilium as a Complex Signaling Center. Curr Biol. 2009;19:R526–35. https://doi.org/10. 1016/j.cub.2009.05.025.

14. Guay-Woodford LM. Renal cystic diseases: Diverse phenotypes converge on the cilium/centrosome complex. Pediatr Nephrol. 2006;21:1369–76.

15. Park TJ, Haigo SL, Wallingford JB. Ciliogenesis defects in embryos lacking inturned or fuzzy function are associated with failure of planar cell polar- ity and Hedgehog signaling. Nat Genet. 2006;38:303–11.

16. Kim SK, Shindo A, Park TJ, Oh EC, Ghosh S, Gray RS, et al. Planar Cell Polarity Acts Through Septins to Control Collective Cell Movement and Ciliogenesis. Science. 2010;329:1337–40. https://doi.org/10.1126/science. 1191184.

17. Han Y, Kim HJ, Dlugosz AA, Ellison DW, Gilbertson RJ, Alvarez-Buylla A. Dual and opposing roles of primary cilia in medulloblastoma develop- ment. Nat Med. 2009;15:1062–5. https://doi.org/10.1038/nm.2020.

18. Reiter JF, Leroux MR. Genes and molecular pathways underpinning cili- opathies. Nat Rev Mol Cell Biol. 2017;18:533–47. https://doi.org/10.1038/ nrm.2017.60.

19. Mitchison HM, Valente EM. Motile and non-motile cilia in human pathol- ogy: from function to phenotypes. J Pathol. 2017;241:294–309.

20. Parisi MA. Clinical and molecular features of Joubert syndrome and related disorders. Am J Med Genet Part C Semin Med Genet. 2009;151:326–40.

21. Brancati F, Dallapiccola B, Valente E. Joubert Syndrome and related disorders. Orphanet J Rare Dis. 2010;5:20. https://doi.org/10.1186/ 1750-1172-5-20.

22. Vertii A, Hung HF, Hehnly H, Doxsey S. Human basal body basics. Cilia. 2016;5:1–7.

23. Winey M, O’Toole E. Centriole structure. Philos Trans R Soc B Biol Sci. 2014;369.

24. Mennella V, Agard DA, Huang B, Pelletier L. Amorphous no more: Subdif- fraction view of the pericentriolar material architecture. Trends Cell Biol. 2014;24:188–97. https://doi.org/10.1016/j.tcb.2013.10.001.

25. Doxsey SJ, Stein P, Evans L, Calarco PD, Kirschner M. Pericentrin, a highly conserved centrosome protein involved in microtubule organization. Cell. 1994;76:639–50. https://doi.org/10.1016/0092-8674(94)90504-5.

26. Woodruff JB, Wueseke O, Hyman AA. Pericentriolar material structure and dynamics. Philos Trans R Soc B Biol Sci. 2014;369.

27. David-Pfeuty T, Erickson HP, Pantaloni D. Guanosinetriphosphatase activ- ity of tubulin associated with microtubule assembly. Proc Natl Acad Sci U S A. 1977;74:5372–6.

28. Babu MM, van der Lee R, de Groot NS, Gsponer J. Intrinsically disordered proteins: Regulation and disease. Curr Opin Struct Biol. 2011;21:432–40.

29. van der Lee R, Buljan M, Lang B, Weatheritt RJ, Daughdrill GW, Dunker AK, et al. Classification of Intrinsically Disordered Regions and Proteins. Chem Rev. 2014;114:6589–631. https://doi.org/10.1021/cr400525m.

30. Wright PE, Dyson HJ. Intrinsically disordered proteins in cellular signalling and regulation. Nat Rev Mol Cell Biol. 2015;16:18–29. https://doi.org/10. 1038/nrm3920.

31. Banani SF, Lee HO, Hyman AA, Rosen MK. Biomolecular condensates: Organizers of cellular biochemistry. Nat Rev Mol Cell Biol. 2017;18:285–98. https://doi.org/10.1038/nrm.2017.7.

32. Woodruff JB, Ferreira Gomes B, Widlund PO, Mahamid J, Honigmann A, Hyman AA. The Centrosome Is a Selective Condensate that Nucleates Microtubules by Concentrating Tubulin. Cell. 2017;169:1066-1077.e10. doi:10.1016/j.cell.2017.05.028.

33. Kelley LA, Mezulis S, Yates CM, Wass MN, Sternberg MJE. The Phyre2 web portal for protein modeling, prediction and analysis. Nat Protoc. 2015;10:845–58. https://doi.org/10.1038/nprot.2015.053.

34. Fernandez EM, Díaz-Ceso MD, Vilar M. Brain Expressed and X-Linked (Bex) Proteins Are Intrinsically Disordered Proteins (IDPs) and Form New Signal- ing Hubs. PLoS One. 2015;10:e0117206. https://doi.org/10.1371/journal. pone.0117206.

35. Hiramatsu N, Hibino E, Matsuzaki K, Kuwahara J, Hoshino M. Interaction between isolated transcriptional activation domains of Sp1 revealed by heteronuclear magnetic resonance. Protein Sci. 2012;21:1481–8.

36. Hibino E, Inoue R, Sugiyama M, Kuwahara J, Matsuzaki K, Hoshino M. Identification of heteromolecular binding sites in transcription factors Sp1 and TAF4 using high-resolution nuclear magnetic resonance spectroscopy. Protein Sci. 2017;26:2280–90. https://doi.org/10.1002/ pro.3287.

37. Wishart DS, Bigam CG, Holm A, Hodges RS, Sykes BD. 1H, 13C and 15N random coil NMR chemical shifts of the common amino acids. I. Investi- gations of nearest-neighbor effects. J Biomol NMR. 1995;5:67–81.

38. Wei T, Baiqu H, Chunxiang L, Zhonghe Z. In situ visualization of rDNA arrangement and its relationship with subnucleolar structural regions in Allium sativum cell nucleolus. J Cell Sci. 2003;116:1117–25. https://doi. org/10.1242/jcs.00323.

39. Boisvert FM, Van Koningsbruggen S, Navascués J, Lamond AI. The multi- functional nucleolus. Nat Rev Mol Cell Biol. 2007;8:574–85.

40. He J-S, Soo P, Evers M, Parsons KM, Hein N, Hannan KM, et al. High- Content Imaging Approaches to Quantitate Stress-Induced Changes in Nucleolar Morphology. Assay Drug Dev Technol. 2018;16:320–32. https:// doi.org/10.1089/adt.2018.861.

41. Choi K, Lee K, Ryu SW, Im M, Kook KH, Choi C. Pirfenidone inhibits transforming growth factor-β1-induced fibrogenesis by blocking nuclear translocation of smads in human retinal pigment epithelial cell line ARPE-19. Mol Vis. 2011;2012(18):1010–20.

42. Lee J, Choi JH, Joo CK. TGF-β1 regulates cell fate during epithelial-mesen- chymal transition by upregulating survivin. Cell Death Dis. 2013;4:1–10.

43. Li H, Wang H, Wang F, Gu Q, Xu X. Snail involves in the transforming growth factor β1-mediated epithelial-mesenchymal transition of retinal pigment epithelial cells. PLoS One. 2011;6.

44. Cong L, Ran FA, Cox D, Lin S, Barretto R, Habib N, et al. Multiplex Genome Engineering Using CRISPR/Cas Systems. Science. 2013;339:819–23. https://doi.org/10.1126/science.1231143.

45. Mali P, Yang L, Esvelt KM, Aach J, Guell M, DiCarlo JE, et al. RNA-Guided Human Genome Engineering via Cas9. Science. 2013;339:823–6. https:// doi.org/10.1126/science.1232033.

46. Inui M, Miyado M, Igarashi M, Tamano M, Kubo A, Yamashita S, et al. Rapid generation of mouse models with defined point mutations by the CRISPR/Cas9 system. Sci Rep. 2015;4:5396. https://doi.org/10.1038/srep0 5396.

47. Waters AM, Beales PL. Ciliopathies: an expanding disease spec- trum. Pediatr Nephrol. 2011;26:1039–56. https://doi.org/10.1007/ s00467-010-1731-7.

48. Hildebrandt F, Benzing T, Katsanis N. Ciliopathies. N Engl J Med. 2011;364:1533–43. https://doi.org/10.1056/NEJMra1010172.

49. Simms RJ, Hynes AM, Eley L, Sayer JA. Nephronophthisis: A Genetically Diverse Ciliopathy. Int J Nephrol. 2011;2011:1–10. https://doi.org/10.4061/ 2011/527137.

50. Nishiyama K, Sakaguchi H, Hu JG, Bok D, Hollyfield JG. Claudin localization in cilia of the retinal pigment epithelium. Anat Rec. 2002;267:196–203. https://doi.org/10.1002/ar.10102.

51. Wheway G, Parry DA, Johnson CA. The role of primary cilia in the devel- opment and disease of the retina. Organogenesis. 2014;10:69–85. https:// doi.org/10.4161/org.26710.

52. May-Simera HL, Wan Q, Jha BS, Hartford J, Khristov V, Dejene R, et al. Primary Cilium-Mediated Retinal Pigment Epithelium Maturation Is Disrupted in Ciliopathy Patient Cells. Cell Rep. 2018;22:189–205. https:// doi.org/10.1016/j.celrep.2017.12.038.

53. Chizhikov VV, Davenport J, Zhang Q, Shih EK, Cabello OA, Fuchs JL, et al. Cilia Proteins Control Cerebellar Morphogenesis by Promoting Expansion of the Granule Progenitor Pool. J Neurosci. 2007;27:9780–9. https://doi. org/10.1523/JNEUROSCI.5586-06.2007.

54. Spassky N, Han Y-G, Aguilar A, Strehl L, Besse L, Laclef C, et al. Primary cilia are required for cerebellar development and Shh-dependent expansion of progenitor pool. Dev Biol. 2008;317:246–59. https://doi.org/10.1016/j. ydbio.2008.02.026.

55. Karp NA, Mason J, Beaudet AL, Benjamini Y, Bower L, Braun RE, et al. Prevalence of sexual dimorphism in mammalian phenotypic traits. Nat Commun. 2017;8.

56. Huizar RL, Lee C, Boulgakov AA, Horani A, Tu F, Marcotte EM, et al. A liquid-like organelle at the root of motile ciliopathy. Elife. 2018;7:1–24.

57. Patnaik SR. Kretschmer V, Brücker L, Schneider S, Volz AK, Oancea-Castillo L del R, et al. Bardet–Biedl Syndrome proteins regulate cilia disassembly during tissue maturation. Cell Mol Life Sci. 2019;76:757–75. https://doi. org/10.1007/s00018-018-2966-x.

58. Parisi MA. The molecular genetics of Joubert syndrome and related cili- opathies: The challenges of genetic and phenotypic heterogeneity. Transl Sci Rare Dis. 2019;4:25–49.

59. Choksi SP, Lauter G, Swoboda P, Roy S. Switching on cilia: Transcriptional networks regulating ciliogenesis. Dev. 2014;141:1427–41.

60. Bujakowska KM, Liu Q, Pierce EA. Photoreceptor Cilia and Retinal Ciliopa- thies. Cold Spring Harb Perspect Biol. 2017;9:a028274. https://doi.org/10. 1101/cshperspect.a028274.

61. May-Simera HL, Gumerson JD, Gao C, Campos M, Cologna SM, Beyer T, et al. Loss of MACF1 Abolishes Ciliogenesis and Disrupts Apicobasal Polarity Establishment in the Retina. Cell Rep. 2016;17:1399–413. https:// doi.org/10.1016/j.celrep.2016.09.089.

62. Grisanti L, Revenkova E, Gordon RE, Iomini C. Primary cilia maintain cor- neal epithelial homeostasis by regulation of the Notch signaling pathway. Development. 2016;143:2160–71. https://doi.org/10.1242/dev.132704.

63. Blitzer AL, Panagis L, Gusella GL, Danias J, Mlodzik M, Iomini C. Primary cilia dynamics instruct tissue patterning and repair of corneal endothe- lium. Proc Natl Acad Sci U S A. 2011;108:2819–24.

64. Bisgrove BW, Yost HJ. The roles of cilia in developmental disorders and disease. Development. 2006;133:4131–43.

65. Field D, Tiwari B, Booth T, Houten S, Swan D, Bertrand N, et al. Open soft- ware for biologists: from famine to feast. Nat Biotechnol. 2006;24:801–3. https://doi.org/10.1038/nbt0706-801.

66. Schindelin J, Arganda-Carreras I, Frise E, Kaynig V, Longair M, Pietzsch T, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9:676–82. https://doi.org/10.1038/nmeth.2019.

参考文献をもっと見る

全国の大学の
卒論・修論・学位論文

一発検索!

この論文の関連論文を見る