Analysis of Meiosis in SUN1 Deficient Mice Reveals a Distinct Role of SUN2 in Mammalian Meiotic LINC Complex Formation and Function

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LINC complexes are evolutionarily conserved nuclear envelope bridges, composed of SUN (Sad-1/UNC-84) and KASH (Klarsicht/ANC-1/Syne/homology) domain proteins. They are crucial for nuclear positioning and nuclear shape determination, and also mediate nuclear envelope (NE) attachment of meiotic telomeres, essential for driving homolog synapsis and recombination. In mice, SUN1 and SUN2 are the only SUN domain proteins expressed during meiosis, sharing their localization with meiosis-specific KASH5. Recent studies have shown that loss of SUN1 severely interferes with meiotic processes. Absence of SUN1 provokes defective telomere attachment and causes infertility. Here, we report that meiotic telomere attachment is not entirely lost in mice deficient for SUN1, but numerous telomeres are still attached to the NE through SUN2/KASH5-LINC complexes. In Sun1^−/− meiocytes attached telomeres retained the capacity to form bouquet-like clusters. Furthermore, we could detect significant numbers of late meiotic recombination events in Sun1^−/− mice. Together, this indicates that even in the absence of SUN1 telomere attachment and their movement within the nuclear envelope per se can be functional.

Vyšlo v časopise: Analysis of Meiosis in SUN1 Deficient Mice Reveals a Distinct Role of SUN2 in Mammalian Meiotic LINC Complex Formation and Function. PLoS Genet 10(2): e32767. doi:10.1371/journal.pgen.1004099
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004099

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Zdroje

1. StarrDA (2009) A nuclear-envelope bridge positions nuclei and moves chromosomes. J Cell Sci 122: 577–586.

2. RothballerA, KutayU (2013) The diverse functional LINCs of the nuclear envelope to the cytoskeleton and chromatin. Chromosoma 122(5): 415–29.

3. CrispM, LiuQ, RouxK, RattnerJB, ShanahanC, et al. (2006) Coupling of the nucleus and cytoplasm: role of the LINC complex. J Cell Biol 172: 41–53.

4. StarrDA, FridolfssonHN (2010) Interactions between nuclei and the cytoskeleton are mediated by SUN-KASH nuclear-envelope bridges. Annu Rev Cell Dev Biol 26: 421–444.

5. RazafskyD, HodzicD (2009) Bringing KASH under the SUN: the many faces of nucleo-cytoskeletal connections. J Cell Biol 186: 461–472.

6. LombardiML, JaaloukDE, ShanahanCM, BurkeB, RouxKJ, et al. (2011) The interaction between nesprins and sun proteins at the nuclear envelope is critical for force transmission between the nucleus and cytoskeleton. J Biol Chem 286: 26743–26753.

7. MejatA, MisteliT (2010) LINC complexes in health and disease. Nucleus 1: 40–52.

8. KoszulR, KlecknerN (2009) Dynamic chromosome movements during meiosis: a way to eliminate unwanted connections? Trends Cell Biol 19: 716–724.

9. ScherthanH, WeichS, SchweglerH, HeytingC, HarleM, et al. (1996) Centromere and telomere movements during early meiotic prophase of mouse and man are associated with the onset of chromosome pairing. J Cell Biol 134: 1109–1125.

10. YuanL, LiuJG, ZhaoJ, BrundellE, DaneholtB, et al. (2000) The murine SCP3 gene is required for synaptonemal complex assembly, chromosome synapsis, and male fertility. Mol Cell 5: 73–83.

11. DingX, XuR, YuJ, XuT, ZhuangY, et al. (2007) SUN1 is required for telomere attachment to nuclear envelope and gametogenesis in mice. Dev Cell 12: 863–872.

12. SchrammS, FrauneJ, NaumannR, Hernandez-HernandezA, HoogC, et al. (2011) A novel mouse synaptonemal complex protein is essential for loading of central element proteins, recombination, and fertility. PLoS Genet 7: e1002088.

13. LinkJ, JahnD, SchmittJ, GöbE, BaarJ, et al. (2013) The meiotic nuclear lamina regulates chromosome dynamics and promotes efficient homologous recombination in the mouse. PLoS Genet 9: e1003261.

14. ChikashigeY, TsutsumiC, YamaneM, OkamasaK, HaraguchiT, et al. (2006) Meiotic proteins bqt1 and bqt2 tether telomeres to form the bouquet arrangement of chromosomes. Cell 125: 59–69.

15. ChikashigeY, YamaneM, OkamasaK, TsutsumiC, KojidaniT, et al. (2009) Membrane proteins Bqt3 and -4 anchor telomeres to the nuclear envelope to ensure chromosomal bouquet formation. J Cell Biol 187: 413–427.

16. HiraokaY, DernburgAF (2009) The SUN rises on meiotic chromosome dynamics. Dev Cell 17: 598–605.

17. MikiF, KurabayashiA, TangeY, OkazakiK, ShimanukiM, et al. (2004) Two-hybrid search for proteins that interact with Sad1 and Kms1, two membrane-bound components of the spindle pole body in fission yeast. Molecular genetics and genomics : MGG 270: 449–461.

18. WanatJJ, KimKP, KoszulR, ZandersS, WeinerB, et al. (2008) Csm4, in collaboration with Ndj1, mediates telomere-led chromosome dynamics and recombination during yeast meiosis. PLoS Genet 4: e1000188.

19. ConradMN, LeeCY, ChaoG, ShinoharaM, KosakaH, et al. (2008) Rapid telomere movement in meiotic prophase is promoted by NDJ1, MPS3, and CSM4 and is modulated by recombination. Cell 133: 1175–1187.

20. MinnIL, RollsMM, Hanna-RoseW, MaloneCJ (2009) SUN-1 and ZYG-12, mediators of centrosome-nucleus attachment, are a functional SUN/KASH pair in Caenorhabditis elegans. Mol Biol Cell 20: 4586–4595.

21. ChiYH, ChengLI, MyersT, WardJM, WilliamsE, et al. (2009) Requirement for Sun1 in the expression of meiotic reproductive genes and piRNA. Development 136: 965–973.

22. SchmittJ, BenaventeR, HodzicD, HoogC, StewartCL, et al. (2007) Transmembrane protein Sun2 is involved in tethering mammalian meiotic telomeres to the nuclear envelope. Proc Natl Acad Sci U S A 104: 7426–7431.

23. MorimotoA, ShibuyaH, ZhuX, KimJ, IshiguroK, et al. (2012) A conserved KASH domain protein associates with telomeres, SUN1, and dynactin during mammalian meiosis. J Cell Biol 198: 165–172.

24. HornHF, KimDI, WrightGD, WongES, StewartCL, et al. (2013) A mammalian KASH domain protein coupling meiotic chromosomes to the cytoskeleton. J Cell Biol 202: 1023–1039.

25. LeiK, ZhangX, DingX, GuoX, ChenM, et al. (2009) SUN1 and SUN2 play critical but partially redundant roles in anchoring nuclei in skeletal muscle cells in mice. Proc Natl Acad Sci U S A 106: 10207–10212.

26. YuJ, LeiK, ZhouM, CraftCM, XuG, et al. (2011) KASH protein Syne-2/Nesprin-2 and SUN proteins SUN1/2 mediate nuclear migration during mammalian retinal development. Hum Mol Genet 20: 1061–1073.

27. GöbE, SchmittJ, BenaventeR, AlsheimerM (2010) Mammalian sperm head formation involves different polarization of two novel LINC complexes. PLoS One 5: e12072.

28. BellveAR, CavicchiaJC, MilletteCF, O'BrienDA, BhatnagarYM, et al. (1977) Spermatogenic cells of the prepuberal mouse. Isolation and morphological characterization. J Cell Biol 74: 68–85.

29. FrauneJ, SchrammS, AlsheimerM, BenaventeR (2012) The mammalian synaptonemal complex: protein components, assembly and role in meiotic recombination. Exp Cell Res 318: 1340–1346.

30. SosaBA, RothballerA, KutayU, SchwartzTU (2012) LINC complexes form by binding of three KASH peptides to domain interfaces of trimeric SUN proteins. Cell 149: 1035–1047.

31. LuW, GotzmannJ, SironiL, JaegerVM, SchneiderM, et al. (2008) Sun1 forms immobile macromolecular assemblies at the nuclear envelope. Biochim Biophys Acta 1783: 2415–2426.

32. WangQ, DuX, CaiZ, GreeneMI (2006) Characterization of the structures involved in localization of the SUN proteins to the nuclear envelope and the centrosome. DNA and cell biology 25: 554–562.

33. AdelfalkC, JanschekJ, RevenkovaE, BleiC, LiebeB, et al. (2009) Cohesin SMC1beta protects telomeres in meiocytes. J Cell Biol 187: 185–199.

34. VieraA, RufasJS, MartinezI, BarberoJL, OrtegaS, et al. (2009) CDK2 is required for proper homologous pairing, recombination and sex-body formation during male mouse meiosis. J Cell Sci 122: 2149–2159.