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SUN-domain proteins: 'Velcro' that links the nucleoskeleton to the cytoskeleton

Abstract

The novel SUN-domain family of nuclear envelope proteins interacts with various KASH-domain partners to form SUN-domain-dependent 'bridges' across the inner and outer nuclear membranes. These bridges physically connect the nucleus to every major component of the cytoskeleton. SUN-domain proteins have diverse roles in nuclear positioning, centrosome localization, germ-cell development, telomere positioning and apoptosis. By serving both as mechanical adaptors and nuclear envelope receptors, we propose that SUN-domain proteins connect cytoplasmic and nucleoplasmic activities.

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Figure 1: Phylogenetic relationships among SUN-domain proteins.
Figure 2: Known functional domains in SUN-domain proteins.
Figure 3: Models for mechanical bridging of the nuclear envelope by SUN-domain proteins.

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References

  1. Stuurman, N., Heins, S. & Aebi, U. Nuclear lamins: their structure, assembly, and interactions. J. Struct. Biol. 122, 42–66 (1998).

    Article  CAS  PubMed  Google Scholar 

  2. Dahl, K. N., Kahn, S. M., Wilson, K. L. & Discher, D. E. The nuclear envelope lamina network has elasticity and a compressibility limit suggestive of a molecular shock absorber. J. Cell Sci. 117, 4779–4786 (2004).

    Article  CAS  PubMed  Google Scholar 

  3. Lammerding, J. et al. Lamin A/C deficiency causes defective nuclear mechanics and mechanotransduction. J. Clin. Invest. 113, 370–378 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Gruenbaum, Y., Margalit, A., Shumaker, D. K. & Wilson, K. L. The nuclear lamina comes of age. Nature Rev. Mol. Cell Biol. 6, 21–31 (2005).

    Article  CAS  Google Scholar 

  5. Schirmer, E. C., Florens, L., Guan, T., Yates, J. R. & Gerace, L. Nuclear membrane proteins with potential disease links found by subtractive proteomics. Science 531, 1380–1382 (2003).

    Article  Google Scholar 

  6. Gruenbaum, Y. et al. The nuclear lamina and its functions in the nucleus. Int. Rev. Cyt. 226, 1–62 (2003).

    Article  CAS  Google Scholar 

  7. Worman, H. J. Inner nuclear membrane and signal transduction. J. Cell Biochem. 96, 1185–1192 (2005).

    Article  CAS  PubMed  Google Scholar 

  8. Starr, D. A. & Fischer, J. A. KASH 'n Karry: the KASH domain family of cargo-specific cytoskeletal adaptor proteins. Bioessays 27, 1136–1146 (2005).

    Article  CAS  PubMed  Google Scholar 

  9. Warren, D. T., Zhang, Q., Weissberg, P. L. & Shanahan, C. M. Nesprins: intracellular scaffolds that maintain cell architecture and coordinate cell function? Expert. Rev. Mol. Med. 7, 1–15 (2005).

    Article  PubMed  Google Scholar 

  10. McGee, M. D., Rillo, R., Anderson, A. S. & Starr, D. A. UNC-83 Is a KASH protein required for nuclear migration and is recruited to the outer nuclear membrane by a physical interaction with the SUN protein UNC-84. Mol. Biol. Cell 17, 1790–1801 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Padmakumar, V. C. et al. The inner nuclear membrane protein Sun1 mediates the anchorage of Nesprin-2 to the nuclear envelope. J. Cell Sci. 118, 3419–3430 (2005).

    Article  CAS  PubMed  Google Scholar 

  12. Malone, C. J., Fixsen, W. D., Horvitz, H. R. & Han, M. UNC-84 localizes to the nuclear envelope and is required for nuclear migration and anchoring during C. elegans development. Development 126, 3171–3181 (1999).

    CAS  PubMed  Google Scholar 

  13. Crisp, M. et al. Coupling of the nucleus and cytoplasm: role of the LINC complex. J. Cell Biol. 172, 41–53 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Lee, K. K. et al. Lamin-dependent localization of UNC-84, a protein required for nuclear migration in C. elegans. Mol. Biol. Cell 13, 892–901 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Hasan, S. et al. Nuclear envelope localization of human UNC84A does not require nuclear lamins. FEBS Lett. 580, 1263–1268 (2006).

    Article  CAS  PubMed  Google Scholar 

  16. Hagan, I. & Yanagida, M. The product of the spindle formation gene sad1+ associates with the fission yeast spindle pole body and is essential for viability. J. Cell Biol. 129, 1033–1047 (1995).

    Article  CAS  PubMed  Google Scholar 

  17. Starr, D. A. & Han, M. ANChors away: an actin based mechanism of nuclear positioning. J. Cell Sci. 116, 211–216 (2003).

    Article  CAS  PubMed  Google Scholar 

  18. Fridkin, A. et al. Matefin, a C. elegans germ-line specific SUN-domain nuclear membrane protein, is essential for early embryonic and germ cell development. Proc. Natl Acad. Sci. USA 101, 6987–6992 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Haque, F. et al. SUN1 interacts with nuclear lamin A and cytoplasmic nesprins to provide a physical connection between the nuclear lamina and the cytoskeleton. Mol. Cell. Biol. 26, 3738–3851 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Hodzic, D. M., Yeater, D. B., Bengtsson, L., Otto, H. & Stahl, P. D. Sun2 is a novel mammalian inner nuclear membrane protein. J. Biol. Chem. 279, 25805–25812 (2004).

    Article  CAS  PubMed  Google Scholar 

  21. Zhang, Q. et al. Nesprins: a novel family of spectrin-repeat-containing proteins that localize to the nuclear membrane in multiple tissues. J. Cell Sci. 114, 4485–4498 (2001).

    CAS  PubMed  Google Scholar 

  22. Libotte, T. et al. Lamin A/C-dependent localization of Nesprin-2, a giant scaffolder at the nuclear envelope. Mol. Biol. Cell 16, 3411–3424 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Zhang, Q. et al. Nesprin-2 is a multi-isomeric protein that binds lamin and emerin at the nuclear envelope and forms a subcellular network in skeletal muscle. J. Cell Sci. 118, 673–687 (2005).

    Article  CAS  PubMed  Google Scholar 

  24. Zhang, Q., Ragnauth, C., Greener, J. M., Shanahan, C. M. & Roberts, R. G. The nesprins are giant actin-binding proteins, orthologous to Drosophila muscle protein MSP-300. Genomics 80, 473–481 (2002).

    Article  CAS  PubMed  Google Scholar 

  25. Wilhelmsen, K. et al. Nesprin-3, a novel outer nuclear membrane protein, associates with the cytoskeletal linker protein plectin. J. Cell Biol. 171, 799–810 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Starr, D. A. & Han, M. Role of ANC-1 in tethering nuclei to the actin cytoskeleton. Science 11, 406–409 (2002).

    Article  Google Scholar 

  27. Patterson, K. et al. The functions of Klarsicht and nuclear lamin in developmentally regulated nuclear migrations of photoreceptor cells in the Drosophila eye. Mol. Biol. Cell 15, 600–610 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Fischer, J. A. et al. Drosophila klarsicht has distinct subcellular localization domains for nuclear envelope and microtubule localization in the eye. Genetics 168, 1385–1393 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Mislow, M. K. J. et al. Nesprin-1a self-associates and binds directly to emerin and lamin A in vitro. FEBS Lett. 525, 135–140 (2002).

    Article  CAS  PubMed  Google Scholar 

  30. Muchir, A. et al. Nuclear envelope alterations in fibroblasts from LGMD1B patients carrying nonsense Y259X heterozygous or homozygous mutation in lamin A/C gene. Exp. Cell Res. 291, 352–362 (2003).

    Article  CAS  PubMed  Google Scholar 

  31. Sullivan, T. et al. Loss of A-type lamin expression compromises nuclear envelope integrity leading to muscular dystrophy. J. Cell Biol. 147, 913–920 (1999).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Pare, G. C., Easlick, J. L., Mislow, J. M., McNally, E. M. & Kapiloff, M. S. Nesprin-1α contributes to the targeting of mAKAP to the cardiac myocyte nuclear envelope. Exp. Cell Res. 303, 388–399 (2005).

    Article  CAS  PubMed  Google Scholar 

  33. Yu, J. et al. The KASH domain protein MSP-300 plays an essential role in nuclear anchoring during Drosophila oogenesis. Dev. Biol. 289, 336–345 (2006).

    Article  CAS  PubMed  Google Scholar 

  34. Grady, R. M., Starr, D. A., Ackerman, G. L., Sanes, J. R. & Han, M. Syne proteins anchor muscle nuclei at the neuromuscular junction. Proc. Natl Acad. Sci. USA 102, 4359–4364 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Horvitz, H. R. & Sulston, J. E. Isolation and genetic characterization of cell-lineage mutants of the nematode Caenorhabditis elegans. Genetics 96, 435–454 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  36. Malone, C. J. et al. The C. elegans Hook protein, ZYG-12, mediates the essential attachment between the centrosome and nucleus. Cell 115, 825–836 (2003).

    Article  CAS  PubMed  Google Scholar 

  37. Mislow, J. M., Kim, M. S., Davis, D. B. & McNally, E. M. Myne-1, a spectrin repeat transmembrane protein of the myocyte inner nuclear membrane, interacts with lamin A/C. J. Cell Sci. 115, 61–70 (2002).

    CAS  PubMed  Google Scholar 

  38. Pederson, T. & Aebi, U. Actin in the nucleus: what form and what for? J. Struct. Biol. 140, 3–9 (2002).

    Article  CAS  PubMed  Google Scholar 

  39. Bettinger, B. T., Gilbert, D. M. & Amberg, D. C. Actin up in the nucleus. Nature Rev. Mol. Cell Biol. 5, 410–415 (2004).

    Article  CAS  Google Scholar 

  40. Holaska, J. M., Kowalski, A. K. & Wilson, K. L. Emerin caps the pointed end of actin filaments: evidence for an actin cortical network at the nuclear inner membrane. PLoS Biol. 2, e321 (2004).

    Article  Google Scholar 

  41. Smythe, C., Jenkins, H. E. & Hutchison, C. J. Incorporation of the nuclear pore basket protein Nup153 into nuclear pore structures is dependent upon lamina assembly: evidence from cell-free extracts of Xenopus eggs. EMBO J. 19, 3918–3931 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Greber, U. F. & Gerace, L. Nuclear protein import is inhibited by an antibody to a lumenal epitope of a nuclear pore complex glycoprotein. J. Cell Biol. 116, 15–30 (1992).

    Article  CAS  PubMed  Google Scholar 

  43. Ding, D. Q., Chikashige, Y., Haraguchi, T. & Hiraoka, Y. Oscillatory nuclear movement in fission yeast meiotic prophase is driven by astral microtubules, as revealed by continuous observation of chromosomes and microtubules in living cells. J. Cell Sci. 111, 701–712 (1998).

    CAS  PubMed  Google Scholar 

  44. Chikashige, Y. et al. Meiotic proteins Bqt1 and Bqt2 tether telomeres to form the bouquet arrangement of chromosomes. Cell 125, 59–69 (2006).

    Article  CAS  PubMed  Google Scholar 

  45. Niwa, O., Shimanuki, M. & Miki, F. Telomere-led bouquet formation facilitates homologous chromosome pairing and restricts ectopic interaction in fission yeast meiosis. EMBO J. 19, 3831–3840 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Greer, E. L. & Brunet, A. FOXO transcription factors at the interface between longevity and tumor suppression. Oncogene 24, 7410–7425 (2005).

    Article  CAS  PubMed  Google Scholar 

  47. Worman, H. J. & Courvalin, J. C. Nuclear envelope, nuclear lamina, and inherited disease. Int. Rev. Cytol. 246, 231–279 (2005).

    Article  CAS  PubMed  Google Scholar 

  48. Cohen, M., Lee, K. K., Wilson, K. L. & Gruenbaum, Y. Transcriptional repression, apoptosis, human disease and the functional evolution of the nuclear lamina. Trends Biochem. Sci. 26, 41–47 (2001).

    Article  CAS  PubMed  Google Scholar 

  49. Mattout, A., Dechat, T., Adam, S. A., Goldman, R. D. & Gruenbaum, Y. Nuclear lamins, diseases and aging. Curr. Opin. Cell Biol. 18, 335–341 (2006).

    Article  CAS  PubMed  Google Scholar 

  50. Corrigan, D. P. et al. Prelamin A endoproteolytic processing in vitro by recombinant Zmpste24. Biochem. J. 387, 129–138 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Zastrow, M. S., Vlcek, S. & Wilson, K. L. Proteins that bind A-type lamins: integrating isolated clues. J. Cell Sci. 117, 979–987 (2004).

    Article  CAS  PubMed  Google Scholar 

  52. Goldman, R. D., Gruenbaum, Y., Moir, R. D., Shumaker, D. K. & Spann, T. P. Nuclear lamins: building blocks of nuclear architecture. Genes Dev. 16, 533–547 (2002).

    Article  CAS  PubMed  Google Scholar 

  53. Decostre, V., Ben Yaou, R. & Bonne, G. Laminopathies affecting skeletal and cardiac muscles: clinical and pathophysiological aspects. Acta Myol. 24, 104–109 (2005).

    CAS  PubMed  Google Scholar 

  54. Broers, J. L., Hutchison, C. J. & Ramaekers, F. C. Laminopathies. J. Pathol. 204, 478–488 (2004).

    Article  CAS  PubMed  Google Scholar 

  55. Thompson, J. D., Higgins, D. G. & Gibson, T. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nuc. Acids Res. 22, 4673–4680 (1994).

    Article  CAS  Google Scholar 

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Acknowledgements

We gratefully acknowledge support from the Israel Science Foundation (ISF), Israel–USA Binational Science Foundation (BSF) and the European Union's FP6, Life Science, Genomics and Biotechnology for Health to Y.G., and the National Institutes of Health to K.L.W.

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Correspondence to Katherine L. Wilson or Yosef Gruenbaum.

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Tzur, Y., Wilson, K. & Gruenbaum, Y. SUN-domain proteins: 'Velcro' that links the nucleoskeleton to the cytoskeleton. Nat Rev Mol Cell Biol 7, 782–788 (2006). https://doi.org/10.1038/nrm2003

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