Nexin-Dynein regulatory complex component DRC7 but not FBXL13 is required for sperm flagellum formation and male fertility in mice
Autoři:
Akane Morohoshi aff001; Haruhiko Miyata aff001; Keisuke Shimada aff001; Kaori Nozawa aff001; Takafumi Matsumura aff001; Ryuji Yanase aff004; Kogiku Shiba aff004; Kazuo Inaba aff004; Masahito Ikawa aff001
Působiště autorů:
Research Institute for Microbial Diseases, Osaka University, Osaka, Japan
aff001; Graduate School of Medicine, Osaka University, Osaka, Japan
aff002; Graduate School of Pharmaceutical Sciences, Osaka University, Osaka, Japan
aff003; Shimoda Marine Research Center, University of Tsukuba, Shizuoka, Japan
aff004; The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
aff005
Vyšlo v časopise:
Nexin-Dynein regulatory complex component DRC7 but not FBXL13 is required for sperm flagellum formation and male fertility in mice. PLoS Genet 16(1): e32767. doi:10.1371/journal.pgen.1008585
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pgen.1008585
Souhrn
Flagella and cilia are evolutionarily conserved cellular organelles. Abnormal formation or motility of these organelles in humans causes several syndromic diseases termed ciliopathies. The central component of flagella and cilia is the axoneme that is composed of the ‘9+2’ microtubule arrangement, dynein arms, radial spokes, and the Nexin-Dynein Regulatory Complex (N-DRC). The N-DRC is localized between doublet microtubules and has been extensively studied in the unicellular flagellate Chlamydomonas. Recently, it has been reported that TCTE1 (DRC5), a component of the N-DRC, is essential for proper sperm motility and male fertility in mice. Further, TCTE1 has been shown to interact with FBXL13 (DRC6) and DRC7; however, functional roles of FBXL13 and DRC7 in mammals have not been elucidated. Here we show that Fbxl13 and Drc7 expression are testes-enriched in mice. Although Fbxl13 knockout (KO) mice did not show any obvious phenotypes, Drc7 KO male mice were infertile due to their short immotile spermatozoa. In Drc7 KO spermatids, the axoneme is disorganized and the ‘9+2’ microtubule arrangement was difficult to detect. Further, other N-DRC components fail to incorporate into the flagellum without DRC7. These results indicate that Drc7, but not Fbxl13, is essential for the correct assembly of the N-DRC and flagella.
Klíčová slova:
Cilia – Flagella – Microtubules – Sperm – Spermatids – Spermatogenesis – Sperm head – Flagellar motility
Zdroje
1. Gibbons IR. Cilia and flagella of eukaryotes. J Cell Biol. 1981; 91: 107–124.
2. Satir P, Christensen ST. Overview of Structure and Function of Mammalian Cilia. Annu Rev Physiol. 2007; 69: 377–400. doi: 10.1146/annurev.physiol.69.040705.141236 17009929
3. Carvalho-santos Z, Azimzadeh J, Pereira-leal JB, Bettencourt-dias M. Tracing the origins of centrioles, cilia, and flagella. J Cell Biol. 2011; 195: 341.
4. Fliegauf M, Benzing T, Omran H. When cilia go bad: cilia defects and ciliopathies. Nat Rev Mol Cell Biol. 2007; 8: 880–93. doi: 10.1038/nrm2278 17955020
5. Luck DJL. Genetic and biochemical dissection of the eucaryotic flagellum. J Cell Biol. 1984; 98: 789–794. doi: 10.1083/jcb.98.3.789 6230366
6. Porter ME, Sale WS. The 9 + 2 axoneme anchors multiple inner arm dyneins and a network of kinases and phosphatases that control motility. J Cell Biol. 2000;151: 37–42.
7. Satir P. Studies on cilia. 3. Further studies on the cilium tip and a “sliding filament” model of ciliary motility. J Cell Biol. 1968; 39: 77–94. doi: 10.1083/jcb.39.1.77 5678451
8. Summers KE, Gibbons IR. Adenosine triphosphate-induced sliding of tubules in trypsin-treated flagella of sea-urchin sperm Proc Natl Acad Sci. 1971;68: 3092–3096. doi: 10.1073/pnas.68.12.3092 5289252
9. Yang P, Diener DR, Yang C, Kohno T, Pazour GJ, Dienes JM, et al. Radial spoke proteins of Chlamydomonas flagella. J Cell Sci. 2006; 119: 1165–1174. doi: 10.1242/jcs.02811 16507594
10. Heuser T, Raytchev M, Krell J, Porter ME, Nicastro D. The dynein regulatory complex is the nexin link and a major regulatory node in cilia and flagella. J Cell Biol. 2009; 187: 921–933. doi: 10.1083/jcb.200908067 20008568
11. Oda T, Yanagisawa H, Kikkawa M. Detailed structural and biochemical characterization of the nexin-dynein regulatory complex. Mol Biol Cell. 2015; 26: 294–304. doi: 10.1091/mbc.E14-09-1367 25411337
12. Gardner LC, O'Toole E, Perrone CA, Giddings T, Porter ME. Components of a "dynein regulatory complex" are located at the junction between the radial spokes and the dynein arms in Chlamydomonas flagella. J Cell Biol. 1994; 127: 1311–1325. doi: 10.1083/jcb.127.5.1311 7962092
13. Gui L, Song K, Tritschler D, Bower R, Yan S, Dai A, et al. Scaffold subunits support associated subunit assembly in the Chlamydomonas ciliary nexin–dynein regulatory complex. Proc Natl Acad Sci U S A. 2019; 116: 23152–23162. doi: 10.1073/pnas.1910960116 31659045
14. Lin J, Tritschler D, Song K, Barber CF, Cobb JS, Porter ME, et al. Building blocks of the nexin-dynein regulatory complex in chlamydomonas flagella. J Biol Chem. 2011; 286: 29175–29191. doi: 10.1074/jbc.M111.241760 21700706
15. Bower R, Tritschler D, Vanderwaal K, Perrone CA, Mueller J, Fox L, et al. The N-DRC forms a conserved biochemical complex that maintains outer doublet alignment and limits microtubule sliding in motile axonemes. Mol Biol Cell. 2013; 24:1134–52. doi: 10.1091/mbc.E12-11-0801 23427265
16. Bower R, Tritschler D, Mills KV, Heuser T, Nicastro D, Porter ME. DRC2/CCDC65 is a central hub for assembly of the nexin-dynein regulatory complex and other regulators of ciliary and flagellar motility. Mol Biol Cell. 2018; 29: 137–153. doi: 10.1091/mbc.E17-08-0510 29167384
17. Awata J, Song K, Lin J, King SM, Sanderson MJ, Nicastro D, et al. DRC3 connects the N-DRC to dynein g to regulate flagellar waveform. Mol Biol Cell. 2015; 26: 2788–800. doi: 10.1091/mbc.E15-01-0018 26063732
18. Ralston KS, Lerner AG, Diener DR, Hill KL. Flagellar motility contributes to cytokinesis in Trypanosoma brucei and is modulated by an evolutionarily conserved dynein regulatory system. Eukaryot Cell. 2006; 5: 696–711. doi: 10.1128/EC.5.4.696-711.2006 16607017
19. Kabututu ZP, Thayer M, Melehani JH, Hill KL. CMF70 is a subunit of the dynein regulatory complex. J Cell Sci. 2010; 123(Pt 20): 3587–95. doi: 10.1242/jcs.073817 20876659
20. Nguyen HT, Sandhu J, Langousis G, Hill KL. CMF22 is a broadly conserved axonemal protein and is required for propulsive motility in Trypanosoma brucei. Eukaryot Cell. 2013; 12: 1202–13. doi: 10.1128/EC.00068-13 23851336
21. Colantonio JR, Vermot J, Wu D, Langenbacher AD, Fraser S, Chen JN, et al. The dynein regulatory complex is required for ciliary motility and otolith biogenesis in the inner ear. Nature. 2009; 457: 205–9. doi: 10.1038/nature07520 19043402
22. Wirschell M, Olbrich H, Werner C, Tritschler D, Bower R, Sale WS, et al. The nexin-dynein regulatory complex subunit DRC1 is essential for motile cilia function in algae and humans. Nat Genet. 2013; 45: 262–268. doi: 10.1038/ng.2533 23354437
23. Austin-Tse C, Halbritter J, Zariwala MA, Gilberti RM, Gee HY, Hellman N, et al. Zebrafish ciliopathy screen plus human mutational analysis identifies C21orf59 and CCDC65 defects as causing primary ciliary dyskinesia. Am J Hum Genet. 2013; 93: 672–686. doi: 10.1016/j.ajhg.2013.08.015 24094744
24. Olbrich H, Cremers C, Loges NT, Werner C, Nielsen KG, Marthin JK, et al. Loss-of-Function GAS8 Mutations Cause Primary Ciliary Dyskinesia and Disrupt the Nexin-Dynein Regulatory Complex. Am J Hum Genet. 2015; 97: 546–54. doi: 10.1016/j.ajhg.2015.08.012 26387594
25. Lewis WR, Malarkey EB, Tritschler D, Bower R, Pasek RC, Porath JD, et al. Mutation of Growth Arrest Specific 8 Reveals a Role in Motile Cilia Function and Human Disease. PLoS Genet. 2016; 12: e1006220. doi: 10.1371/journal.pgen.1006220 27472056
26. Ha S, Lindsay AM, Timms AE, Beier DR. Mutations in Dnaaf1 and Lrrc48 Cause Hydrocephalus, Laterality Defects, and Sinusitis in Mice. G3 (Bethesda). 2016; 6: 2479–87.
27. Jeanson L, Thomas L, Copin B, Coste A, Sermet-Gaudelus I, Dastot-Le Moal F et al. Mutations in GAS8, a Gene Encoding a Nexin-Dynein Regulatory Complex Subunit, Cause Primary Ciliary Dyskinesia with Axonemal Disorganization. Hum Mutat. 2016; 37: 776–85. doi: 10.1002/humu.23005 27120127
28. Li R, Tan J, Chen L, Feng J, Liang W, Guo X, et al. Iqcg Is Essential for Sperm Flagellum Formation in Mice. PLoS One. 2014; 9: e98053. doi: 10.1371/journal.pone.0098053 24849454
29. Castaneda JM, Hua R, Miyata H, Oji A, Guo Y, Cheng Y, et al. TCTE1 is a conserved component of the dynein regulatory complex and is required for motility and metabolism in mouse spermatozoa. Proc Natl Acad Sci U S A. 2017;114: 5370–5378.
30. Yang Y, Cochran DA, Gargano MD, King I, Samhat NK, Burger BP, et al. Regulation of flagellar motility by the conserved flagellar protein CG34110/Ccdc135/FAP50. Mol Biol Cell. 2011; 22: 976–87. doi: 10.1091/mbc.E10-04-0331 21289096
31. Kluin PM, Kramer MF, de Rooij DG. Spermatogenesis in the immature mouse proceeds faster than in the adult. Int J Androl. 1982; 5: 282–294. doi: 10.1111/j.1365-2605.1982.tb00257.x 7118267
32. Baker MA, Naumovski N, Hetherington L, Weinberg A, Velkov T, Aitken RJ. Head and flagella subcompartmental proteomic analysis of human spermatozoa. Proteomics. 2013; 13: 61–74. doi: 10.1002/pmic.201200350 23161668
33. Oji A, Noda T, Fujihara Y, Miyata H, Kim YJ, Muto M, et al. CRISPR/Cas9 mediated genome editing in ES cells and its application for chimeric analysis in mice. Sci Rep. 2016; 6: 31666. doi: 10.1038/srep31666 27530713
34. Fujihara Y, Kaseda K, Inoue N, Ikawa M, Okabe M. Production of mouse pups from germline transmission-failed knockout chimeras. Transgenic Res. 2013; 22: 195–200. doi: 10.1007/s11248-012-9635-x 22826106
35. Inaba K, Shiba K. Microscopic analysis of sperm movement: links to mechanisms and protein components. Microscopy (Oxf). 2018; 67: 144–155.
36. Lehti MS, Sironen A. Formation and function of the manchette and flagellum during spermatogenesis. Reproduction. 2016; 151: 43–54.
37. Lehti MS, Kotaja N, Sironen A. Molecular and Cellular Endocrinology KIF3A is essential for sperm tail formation and manchette function. Mol Cell Endocrinol. 2013; 377: 44–55. doi: 10.1016/j.mce.2013.06.030 23831641
38. Liu Y, DeBoer K, de Kretser DM, O'Donnell L, O'Connor AE, Merriner D, et al. LRGUK-1 is required for basal body and manchette function during spermatogenesis and male fertility. PLoS Genet. 2015; 11: e1005090. doi: 10.1371/journal.pgen.1005090 25781171
39. Lehti MS, Zhang F, Kotaja N, Sironen A. SPEF2 functions in microtubule-mediated transport in elongating spermatids to ensure proper male germ cell differentiation. Development. 2017; 144: 2683–2693. doi: 10.1242/dev.152108 28619825
40. Dunleavy JEM, Okuda H, O'Connor AE, Merriner DJ, O'Donnell L, Jamsai D, et al. Katanin-like 2 (KATNAL2) functions in multiple aspects of haploid male germ cell development in the mouse. PLoS Genet. 2017; 13: e1007078. doi: 10.1371/journal.pgen.1007078 29136647
41. Lindemann CB, Lesich KA. Functional Anatomy of the Mammalian Sperm Flagellum. Cytoskeleton (Hoboken). 2016; 73: 652–669.
42. Kubo T, Hou Y, Cochran DA, Witman GB, Oda T. A microtubule-dynein tethering complex regulates the axonemal inner dynein f (I1). Mol Biol Cell. 2018; 29:1060–1074. doi: 10.1091/mbc.E17-11-0689 29540525
43. Han YG, Kwok BH, Kernan MJ. Intraflagellar transport is required in Drosophila to differentiate sensory cilia but not sperm. Curr Biol. 2003; 13: 1679–86. doi: 10.1016/j.cub.2003.08.034 14521833
44. Sarpal R, Todi SV, Sivan-Loukianova E, Shirolikar S, Subramanian N, Raff EC, et al. Drosophila KAP interacts with the kinesin II motor subunit KLP64D to assemble chordotonal sensory cilia, but not sperm tails. Curr Biol. 2003; 13: 1687–96. doi: 10.1016/j.cub.2003.09.025 14521834
45. San Agustin JT, Pazour GJ, Witman GB. Intraflagellar transport is essential for mammalian spermiogenesis but is absent in mature sperm. Mol Biol Cell. 2015; 26:4358–72. doi: 10.1091/mbc.E15-08-0578 26424803
46. Inaba K, Mizuno K. Sperm dysfunction and ciliopathy. Reprod Med Biol. 2015; 15: 77–94. doi: 10.1007/s12522-015-0225-5 29259424
47. Konno A, Shiba K, Cai C, Inaba K. Branchial cilia and sperm flagella recruit distinct axonemal components. PLoS One. 2015; 10: e0126005. doi: 10.1371/journal.pone.0126005 25962172
48. Abbasi F, Miyata H, Shimada K, Morohoshi A, Nozawa K, Matsumura T, et al. RSPH6A is required for sperm flagellum formation and male fertility in mice. J Cell Sci. 2018; 131.
49. Dong FN, Amiri-Yekta A, Martinez G, Saut A, Tek J, Stouvenel L, et al. Absence of CFAP69 Causes Male Infertility due to Multiple Morphological Abnormalities of the Flagella in Human and Mouse. Am J Hum Genet. 2018; 102: 636–648. doi: 10.1016/j.ajhg.2018.03.007 29606301
50. Toyoda Y., Yokoyama M. and Hosi T. Studies on the fertilization of mouse eggs in vitro. Jpn. J. Anim. Reprod. 1971; 16: 152–157.
51. Chávez JC, Hernández-González EO, Wertheimer E, Visconti PE, Darszon A, Treviño CL. Participation of the Cl-/HCO(3)- exchangers SLC26A3 and SLC26A6, the Cl- channel CFTR, and the regulatory factor SLC9A3R1 in mouse sperm capacitation. Biol Reprod. 2012; 86: 1–14.
52. Miyata H, Satouh Y, Mashiko D, Muto M, Nozawa K, Shiba K, et al. Sperm calcineurin inhibition prevents mouse fertility with implications for male contraceptive. Science. 2015; 350: 442–445. doi: 10.1126/science.aad0836 26429887
53. Niwa H, Yamamura K, Miyazaki J. Efficient selection for high-expression transfectants with a novel eukaryotic vector. Gene. 1991; 108:193–9. doi: 10.1016/0378-1119(91)90434-d 1660837
54. Tiscornia G, Singer O, Verma IM. Production and purification of lentiviral vectors. Nat Protoc. 2006; 1: 241–245. doi: 10.1038/nprot.2006.37 17406239
55. Shimada K, Kato H, Miyata H, Ikawa M. Glycerol kinase 2 is essential for proper arrangement of crescent-like mitochondria to form the mitochondrial sheath during mouse spermatogenesis. J Reprod Dev. 201; 65: 155–162.
56. Sasaki K, Shiba K, Nakamura A, Kawano N, Satouh Y, Yamaguchi H, et al. Calaxin is required for cilia-driven determination of vertebrate laterality. Commun Biol. 2019; 2: 226.
57. Kimura Y, Yanagimachi R. Intracytoplasmic sperm injection in the mouse. Biol Reprod. 1995; 52: 709–20. doi: 10.1095/biolreprod52.4.709 7779992
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