Spermatogenesis is a complex process reliant upon interactions between germ cells (GC) and supporting somatic cells. Testicular Sertoli cells (SC) support GCs during maturation through physical attachment, the provision of nutrients, and protection from immunological attack. This role is facilitated by an active cytoskeleton of parallel microtubule arrays that permit transport of nutrients to GCs, as well as translocation of spermatids through the seminiferous epithelium during maturation. It is well established that chemical perturbation of SC microtubule remodelling leads to premature GC exfoliation demonstrating that microtubule remodelling is an essential component of male fertility, yet the genes responsible for this process remain unknown. Using a random ENU mutagenesis approach, we have identified a novel mouse line displaying male-specific infertility, due to a point mutation in the highly conserved ATPase domain of the novel KATANIN p60-related microtubule severing protein Katanin p60 subunit A-like1 (KATNAL1). We demonstrate that Katnal1 is expressed in testicular Sertoli cells (SC) from 15.5 days post-coitum (dpc) and that, consistent with chemical disruption models, loss of function of KATNAL1 leads to male-specific infertility through disruption of SC microtubule dynamics and premature exfoliation of spermatids from the seminiferous epithelium. The identification of KATNAL1 as an essential regulator of male fertility provides a significant novel entry point into advancing our understanding of how SC microtubule dynamics promotes male fertility. Such information will have resonance both for future treatment of male fertility and the development of non-hormonal male contraceptives.
Vyšlo v časopise: KATNAL1 Regulation of Sertoli Cell Microtubule Dynamics Is Essential for Spermiogenesis and Male Fertility. PLoS Genet 8(5): e32767. doi:10.1371/journal.pgen.1002697 Kategorie: Research Article prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002697
1. SharpeRM 1994 Regulation of Spermatogenesis. ENK The Physiology of Reproduction New York Raven Press 1363 1434
2. ChengCYWongEWYanHHMrukDD Regulation of spermatogenesis in the microenvironment of the seminiferous epithelium: new insights and advances. Mol Cell Endocrinol 315 49 56
3. MrukDDChengCY 2004 Sertoli-Sertoli and Sertoli-germ cell interactions and their significance in germ cell movement in the seminiferous epithelium during spermatogenesis. Endocr Rev 25 747 806
4. NeelyMDBoekelheideK 1988 Sertoli cell processes have axoplasmic features: an ordered microtubule distribution and an abundant high molecular weight microtubule-associated protein (cytoplasmic dynein). J Cell Biol 107 1767 1776
5. RedenbachDMBoekelheideK 1994 Microtubules are oriented with their minus-ends directed apically before tight junction formation in rat Sertoli cells. Eur J Cell Biol 65 246 257
6. RedenbachDMVoglAW 1991 Microtubule polarity in Sertoli cells: a model for microtubule-based spermatid transport. Eur J Cell Biol 54 277 290
7. VoglAWVaidKSGuttmanJA 2008 The Sertoli cell cytoskeleton. Adv Exp Med Biol 636 186 211
8. HandelMA 1979 Effects of colchicine on spermiogenesis in the mouse. J Embryol Exp Morphol 51 73 83
9. CorreaLMNakaiMStrandgaardCSHessRAMillerMG 2002 Microtubules of the mouse testis exhibit differential sensitivity to the microtubule disruptors Carbendazim and colchicine. Toxicol Sci 69 175 182
10. MarkelewiczRJJrHallSJBoekelheideK 2004 2,5-hexanedione and carbendazim coexposure synergistically disrupts rat spermatogenesis despite opposing molecular effects on microtubules. Toxicol Sci 80 92 100
11. FlemingSLShankPRBoekelheideK 2003 gamma-Tubulin overexpression in Sertoli cells in vivo: I. Localization to sites of spermatid head attachment and alterations in Sertoli cell microtubule distribution. Biol Reprod 69 310 321
12. FlemingSLShankPRBoekelheideK 2003 gamma-Tubulin overexpression in Sertoli cells in vivo. II: Retention of spermatids, residual bodies, and germ cell apoptosis. Biol Reprod 69 322 330
13. WangFZhangQCaoJHuangQZhuX 2008 The microtubule plus end-binding protein EB1 is involved in Sertoli cell plasticity in testicular seminiferous tubules. Exp Cell Res 314 213 226
14. ErricoABallabioARugarliEI 2002 Spastin, the protein mutated in autosomal dominant hereditary spastic paraplegia, is involved in microtubule dynamics. Hum Mol Genet 11 153 163
15. HazanJFonknechtenNMavelDPaternotteCSamsonD 1999 Spastin, a new AAA protein, is altered in the most frequent form of autosomal dominant spastic paraplegia. Nat Genet 23 296 303
16. AhmadFJYuWMcNallyFJBaasPW 1999 An essential role for katanin in severing microtubules in the neuron. J Cell Biol 145 305 315
17. KarabayAYuWSolowskaJMBairdDHBaasPW 2004 Axonal growth is sensitive to the levels of katanin, a protein that severs microtubules. J Neurosci 24 5778 5788
18. McNallyFJValeRD 1993 Identification of katanin, an ATPase that severs and disassembles stable microtubules. Cell 75 419 429
19. QuarmbyL 2000 Cellular Samurai: katanin and the severing of microtubules. J Cell Sci 113 Pt 16 2821 2827
20. YuWSolowskaJMQiangLKarabayABairdD 2005 Regulation of microtubule severing by katanin subunits during neuronal development. J Neurosci 25 5573 5583
21. HartmanJJValeRD 1999 Microtubule disassembly by ATP-dependent oligomerization of the AAA enzyme katanin. Science 286 782 785
22. RigdenDJLiuHHayesSDUrbeSClagueMJ 2009 Ab initio protein modelling reveals novel human MIT domains. FEBS Lett 583 872 878
23. SonbuchnerTMRathUSharpDJ 2010 KL1 is a novel microtubule severing enzyme that regulates mitotic spindle architecture. Cell Cycle 9 2403 2411
24. TorresJZMillerJJJacksonPK 2009 High-throughput generation of tagged stable cell lines for proteomic analysis. Proteomics 9 2888 2891
25. BluthmannHCicurelLKuntzGWHaedenkampGIllmenseeK 1982 Immunohistochemical localization of mouse testis-specific phosphoglycerate kinase (PGK-2) by monoclonal antibodies. EMBO J 1 479 484
26. De GendtKDenoletEWillemsADanielsVWClinckemalieL 2011 Expression of Tubb3, a beta-tubulin isotype, is regulated by androgens in mouse and rat Sertoli cells. Biol Reprod 85 934 945
27. BarraHSArceCAArgaranaCE 1988 Posttranslational tyrosination/detyrosination of tubulin. Mol Neurobiol 2 133 153
28. VassalEBaretteCFonroseXDupontRSans-SoleilhacE 2006 Miniaturization and validation of a sensitive multiparametric cell-based assay for the concomitant detection of microtubule-destabilizing and microtubule-stabilizing agents. J Biomol Screen 11 377 389
29. KennedyCLO'ConnorAESanchez-PartidaLGHollandMKGoodnowCC 2005 A repository of ENU mutant mouse lines and their potential for male fertility research. Mol Hum Reprod 11 871 880
30. KennedyCLO'BryanMK 2006 N-ethyl-N-nitrosourea (ENU) mutagenesis and male fertility research. Hum Reprod Update 12 293 301
31. McNallyKPBazirganOAMcNallyFJ 2000 Two domains of p80 katanin regulate microtubule severing and spindle pole targeting by p60 katanin. J Cell Sci 113 Pt 9 1623 1633
32. NeuwaldAFAravindLSpougeJLKooninEV 1999 AAA+: A class of chaperone-like ATPases associated with the assembly, operation, and disassembly of protein complexes. Genome Res 9 27 43
33. Toyo-OkaKSasakiSYanoYMoriDKobayashiT 2005 Recruitment of katanin p60 by phosphorylated NDEL1, an LIS1 interacting protein, is essential for mitotic cell division and neuronal migration. Hum Mol Genet 14 3113 3128
34. QiangLYuWAndreadisALuoMBaasPW 2006 Tau protects microtubules in the axon from severing by katanin. J Neurosci 26 3120 3129
35. YuWQiangLSolowskaJMKarabayAKoruluS 2008 The microtubule-severing proteins spastin and katanin participate differently in the formation of axonal branches. Mol Biol Cell 19 1485 1498
36. SolowskaJMMorfiniGFalnikarAHimesBTBradyST 2008 Quantitative and functional analyses of spastin in the nervous system: implications for hereditary spastic paraplegia. J Neurosci 28 2147 2157
37. WoodJDLandersJABingleyMMcDermottCJThomas-McArthurV 2006 The microtubule-severing protein Spastin is essential for axon outgrowth in the zebrafish embryo. Hum Mol Genet 15 2763 2771
38. EvansKJGomesERReisenweberSMGundersenGGLauringBP 2005 Linking axonal degeneration to microtubule remodeling by Spastin-mediated microtubule severing. J Cell Biol 168 599 606
39. ErricoAClaudianiPD'AddioMRugarliEI 2004 Spastin interacts with the centrosomal protein NA14, and is enriched in the spindle pole, the midbody and the distal axon. Hum Mol Genet 13 2121 2132
40. BusterDMcNallyKMcNallyFJ 2002 Katanin inhibition prevents the redistribution of gamma-tubulin at mitosis. J Cell Sci 115 1083 1092
41. HartmanJJMahrJMcNallyKOkawaKIwamatsuA 1998 Katanin, a microtubule-severing protein, is a novel AAA ATPase that targets to the centrosome using a WD40-containing subunit. Cell 93 277 287
42. McNallyFJOkawaKIwamatsuAValeRD 1996 Katanin, the microtubule-severing ATPase, is concentrated at centrosomes. J Cell Sci 109 Pt 3 561 567
43. McNallyKAudhyaAOegemaKMcNallyFJ 2006 Katanin controls mitotic and meiotic spindle length. J Cell Biol 175 881 891
44. BaasPWKarabayAQiangL 2005 Microtubules cut and run. Trends Cell Biol 15 518 524
45. Roll-MecakAValeRD 2006 Making more microtubules by severing: a common theme of noncentrosomal microtubule arrays? J Cell Biol 175 849 851
46. WelshMSaundersPTAtanassovaNSharpeRMSmithLB 2009 Androgen action via testicular peritubular myoid cells is essential for male fertility. FASEB J 23 4218 4230
47. WelshMSaundersPTMarchettiNISharpeRM 2006 Androgen-dependent mechanisms of Wolffian duct development and their perturbation by flutamide. Endocrinology 147 4820 4830
48. O'HaraLWelshMSaundersPTSmithLB 2011 Androgen receptor expression in the caput epididymal epithelium is essential for development of the initial segment and epididymal spermatozoa transit. Endocrinology 152 718 729
49. De GendtKSwinnenJVSaundersPTSchoonjansLDewerchinM 2004 A Sertoli cell-selective knockout of the androgen receptor causes spermatogenic arrest in meiosis. Proc Natl Acad Sci U S A 101 1327 1332
Zvýšte si kvalifikáciu online z pohodlia domova
Nemáte účet? Registrujte sa
Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.
