MNS1 Is Essential for Spermiogenesis and Motile Ciliary Functions in Mice

English version České info

During spermiogenesis, haploid round spermatids undergo dramatic cell differentiation and morphogenesis to give rise to mature spermatozoa for fertilization, including nuclear elongation, chromatin remodeling, acrosome formation, and development of flagella. The molecular mechanisms underlining these fundamental processes remain poorly understood. Here, we report that MNS1, a coiled-coil protein of unknown function, is essential for spermiogenesis. We find that MNS1 is expressed in the germ cells in the testes and localizes to sperm flagella in a detergent-resistant manner, indicating that it is an integral component of flagella. MNS1–deficient males are sterile, as they exhibit a sharp reduction in sperm production and the remnant sperm are immotile with abnormal short tails. In MNS1–deficient sperm flagella, the characteristic arrangement of “9+2” microtubules and outer dense fibers are completely disrupted. In addition, MNS1–deficient mice display situs inversus and hydrocephalus. MNS1–deficient tracheal motile cilia lack some outer dynein arms in the axoneme. Moreover, MNS1 monomers interact with each other and are able to form polymers in cultured somatic cells. These results demonstrate that MNS1 is essential for spermiogenesis, the assembly of sperm flagella, and motile ciliary functions.

Vyšlo v časopise: MNS1 Is Essential for Spermiogenesis and Motile Ciliary Functions in Mice. PLoS Genet 8(3): e32767. doi:10.1371/journal.pgen.1002516
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002516

Souhrn

Zdroje

1. SharpeRM 1993 Regulation of spermatogenesis. KnobilENeillJD The Physiology of Reproduction New York Raven Press 1363 1434

2. EddyEMO'BrienDA 1993 The spermatozoon. KnobilENeillJD The Physiology of Reproduction New York Raven Press 29 77

3. YanagimachiR 1993 Mammalian fertilization. KnobilENeillJD The physiology of reproduction New York Raven Press 189 317

4. ChemesHERaweVY 2010 The making of abnormal spermatozoa: Cellular and molecular mechanisms underlying pathological spermiogenesis. Cell Tissue Res 341 349 357

5. InglisPNBoroevichKALerouxMR 2006 Piecing together a ciliome. Trends Genet 22 491 500

6. FliegaufMBenzingTOmranH 2007 When cilia go bad: Cilia defects and ciliopathies. Nat Rev Mol Cell Biol 8 880 893

7. ZariwalaMAKnowlesMROmranH 2007 Genetic defects in ciliary structure and function. Annu Rev Physiol 69 423 450

8. Ibanez-TallonIPagenstecherAFliegaufMOlbrichHKispertA 2004 Dysfunction of axonemal dynein heavy chain Mdnah5 inhibits ependymal flow and reveals a novel mechanism for hydrocephalus formation. Hum Mol Genet 13 2133 2141

9. SapiroRKostetskiiIOlds-ClarkePGertonGLRadiceGL 2002 Male infertility, impaired sperm motility, and hydrocephalus in mice deficient in sperm-associated antigen 6. Mol Cell Biol 22 6298 6305

10. SironenAKotajaNMulhernHWyattTASissonJH 2011 Loss of SPEF2 function in mice results in spermatogenesis defects and primary ciliary dyskinesia. Biol Reprod 85 690 701

11. NonakaSShiratoriHSaijohYHamadaH 2002 Determination of left-right patterning of the mouse embryo by artificial nodal flow. Nature 418 96 99

12. McGrathJSomloSMakovaSTianXBruecknerM 2003 Two populations of node monocilia initiate left-right asymmetry in the mouse. Cell 114 61 73

13. PennarunGEscudierEChapelinCBridouxAMCacheuxV 1999 Loss-of-function mutations in a human gene related to chlamydomonas reinhardtii dynein IC78 result in primary ciliary dyskinesia. Am J Hum Genet 65 1508 1519

14. Becker-HeckAZohnIEOkabeNPollockALenhartKB 2011 The coiled-coil domain containing protein CCDC40 is essential for motile cilia function and left-right axis formation. Nat Genet 43 79 84

15. MerveilleACDavisEEBecker-HeckALegendreMAmiravI 2011 CCDC39 is required for assembly of inner dynein arms and the dynein regulatory complex and for normal ciliary motility in humans and dogs. Nat Genet 43 72 78

16. LeeLCampagnaDRPinkusJLMulhernHWyattTA 2008 Primary ciliary dyskinesia in mice lacking the novel ciliary protein Pcdp1. Mol Cell Biol 28 949 957

17. BartoloniLBlouinJLPanYGehrigCMaitiAK 2002 Mutations in the DNAH11 (axonemal heavy chain dynein type 11) gene cause one form of situs inversus totalis and most likely primary ciliary dyskinesia. Proc Natl Acad Sci U S A 99 10282 10286

18. Ibanez-TallonIGorokhovaSHeintzN 2002 Loss of function of axonemal dynein Mdnah5 causes primary ciliary dyskinesia and hydrocephalus. Hum Mol Genet 11 715 721

19. OlbrichHHaffnerKKispertAVolkelAVolzA 2002 Mutations in DNAH5 cause primary ciliary dyskinesia and randomization of left-right asymmetry. Nat Genet 30 143 144

20. FurukawaKInagakiHNarugeTTabataSTomidaT 1994 cDNA cloning and functional characterization of a meiosis-specific protein (MNS1) with apparent nuclear association. Chromosome Res 2 99 113

21. CarreraAMoosJNingXPGertonGLTesarikJ 1996 Regulation of protein tyrosine phosphorylation in human sperm by a calcium/calmodulin-dependent mechanism: Identification of A kinase anchor proteins as major substrates for tyrosine phosphorylation. Dev Biol 180 284 296

22. CaoWGertonGLMossSB 2006 Proteomic profiling of accessory structures from the mouse sperm flagellum. Mol Cell Proteomics 5 801 810

23. CarreraAGertonGLMossSB 1994 The major fibrous sheath polypeptide of mouse sperm: Structural and functional similarities to the A-kinase anchoring proteins. Dev Biol 165 272 284

24. HuangfuDLiuARakemanASMurciaNSNiswanderL 2003 Hedgehog signalling in the mouse requires intraflagellar transport proteins. Nature 426 83 87

25. GerminoGG 2005 Linking cilia to wnts. Nat Genet 37 455 457

26. OstrowskiLEBlackburnKRaddeKMMoyerMBSchlatzerDM 2002 A proteomic analysis of human cilia: Identification of novel components. Mol Cell Proteomics 1 451 465

27. ZhangZShenXGudeDRWilkinsonBMJusticeMJ 2009 MEIG1 is essential for spermiogenesis in mice. Proc Natl Acad Sci U S A 106 17055 17060

28. SalzbergYEldarTKarminskyODItachSBPietrokovskiS 2010 Meig1 deficiency causes a severe defect in mouse spermatogenesis. Dev Biol 338 158 167

29. LorenzettiDBishopCEJusticeMJ 2004 Deletion of the parkin coregulated gene causes male sterility in the quaking(viable) mouse mutant. Proc Natl Acad Sci U S A 101 8402 8407

30. BennettWIGallAMSouthardJLSidmanRL 1971 Abnormal spermiogenesis in quaking, a myelin-deficient mutant mouse. Biol Reprod 5 30 58

31. SironenAThomsenBAnderssonMAholaVVilkkiJ 2006 An intronic insertion in KPL2 results in aberrant splicing and causes the immotile short-tail sperm defect in the pig. Proc Natl Acad Sci U S A 103 5006 5011

32. PazourGJAgrinNLeszykJWitmanGB 2005 Proteomic analysis of a eukaryotic cilium. J Cell Biol 170 103 113

33. StolcVSamantaMPTongprasitWMarshallWF 2005 Genome-wide transcriptional analysis of flagellar regeneration in chlamydomonas reinhardtii identifies orthologs of ciliary disease genes. Proc Natl Acad Sci U S A 102 3703 3707

34. LiJBGerdesJMHaycraftCJFanYTeslovichTM 2004 Comparative genomics identifies a flagellar and basal body proteome that includes the BBS5 human disease gene. Cell 117 541 552

35. EfimenkoEBubbKMakHYHolzmanTLerouxMR 2005 Analysis of xbx genes in C. elegans. Development 132 1923 1934

36. BlacqueOEPerensEABoroevichKAInglisPNLiC 2005 Functional genomics of the cilium, a sensory organelle. Curr Biol 15 935 941

37. RossAJDaileyLABrightonLEDevlinRB 2007 Transcriptional profiling of mucociliary differentiation in human airway epithelial cells. Am J Respir Cell Mol Biol 37 169 185

38. DuriezBDuquesnoyPEscudierEBridouxAMEscalierD 2007 A common variant in combination with a nonsense mutation in a member of the thioredoxin family causes primary ciliary dyskinesia. Proc Natl Acad Sci U S A 104 3336 3341

39. HarlowELaneD 1998 Using antibodies: A laboratory manual Cold Spring Harbor Cold Spring Harbor Laboratory Press

40. YangFDe La FuenteRLeuNABaumannCMcLaughlinKJ 2006 Mouse SYCP2 is required for synaptonemal complex assembly and chromosomal synapsis during male meiosis. J Cell Biol 173 497 507

41. PanJGoodheartMChumaSNakatsujiNPageDC 2005 RNF17, a component of the mammalian germ cell nuage, is essential for spermiogenesis. Development 132 4029 4039

42. ZhouJPanJEckardtSLeuNAMcLaughlinKJ 2011 Nxf3 is expressed in sertoli cells, but is dispensable for spermatogenesis. Mol Reprod Dev 78 241 249

43. ReddiPPNaaby-HansenSAguolnikITsaiJYSilverLM 1995 Complementary deoxyribonucleic acid cloning and characterization of mSP-10: The mouse homologue of human acrosomal protein SP-10. Biol Reprod 53 873 881

44. StankerLHWyrobekABalhornR 1987 Monoclonal antibodies to human protamines. Hybridoma 6 293 303