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Spermatid differentiation requires the assembly of a cell polarity complex downstream of junctional adhesion molecule-C

Abstract

During spermatogenesis in the mammalian testis, stem cells (spermatogonia) differentiate into spermatocytes, which subsequently undergo two consecutive meiotic divisions to give rise to haploid spermatids. These cells are initially round but progressively elongate, condense their nuclei, acquire flagellar and acrosomal structures, and shed a significant amount of their cytoplasm to form spermatozoa (the sperm cells) in a developmental cascade termed spermiogenesis1,2. Defects in these processes will lead to a lack of mature sperm cells (azoospermia), which is a major cause of male infertility in the human population3. Here we report that a cell-surface protein of the immunoglobulin superfamily, junctional adhesion molecule-C (JAM-C), is critically required for the differentiation of round spermatids into spermatozoa in mice. We found that Jam-C is essential for the polarization of round spermatids, a function that we attribute to its role in the assembly of a cell polarity complex.

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Figure 1: Defective spermiogenesis in Jam-C-/- mutants.
Figure 2: Differentiation arrest of Jam-C-/- spermatids.
Figure 3: Compromised cell polarization in Jam-C KOs.
Figure 4: Cell polarity protein recruitment.

References

  1. Cheng, C. Y. & Mruk, D. D. Cell junction dynamics in the testis: Sertoli-germ cell interactions and male contraceptive development. Physiol. Rev. 82, 825–874 (2002)

    CAS  Article  PubMed  Google Scholar 

  2. Griswold, M. D. Interactions between germ cells and Sertoli cells in the testis. Biol. Reprod. 52, 211–216 (1995)

    CAS  Article  PubMed  Google Scholar 

  3. Ezeh, U. I. Beyond the clinical classification of azoospermia: opinion. Hum. Reprod. 15, 2356–2359 (2000)

    CAS  Article  PubMed  Google Scholar 

  4. Muller, W. A. Leukocyte–endothelial-cell interactions in leukocyte transmigration and the inflammatory response. Trends Immunol. 24, 327–334 (2003)

    CAS  PubMed  Google Scholar 

  5. Aurrand-Lions, M., Johnson-Leger, C. & Imhof, B. A. Role of interendothelial adhesion molecules in the control of vascular functions. Vascul. Pharmacol. 39, 239–246 (2002)

    CAS  Article  PubMed  Google Scholar 

  6. Chavakis, T., Preissner, K. T. & Santoso, S. Leukocyte trans-endothelial migration: JAMs add new pieces to the puzzle. Thromb. Haemost. 89, 13–17 (2003)

    CAS  Article  PubMed  Google Scholar 

  7. Bazzoni, G. The JAM family of junctional adhesion molecules. Curr. Opin. Cell Biol. 15, 525–530 (2003)

    CAS  Article  PubMed  Google Scholar 

  8. Ebnet, K., Suzuki, A., Ohno, S. & Vestweber, D. Junctional adhesion molecules (JAMs): more molecules with dual functions? J. Cell Sci. 117, 19–29 (2004)

    CAS  Article  PubMed  Google Scholar 

  9. Liang, T. W. et al. Vascular endothelial-junctional adhesion molecule (VE-JAM)/JAM 2 interacts with T, NK, and dendritic cells through JAM 3. J. Immunol. 168, 1618–1626 (2002)

    CAS  Article  PubMed  Google Scholar 

  10. Arrate, M. P., Rodriguez, J. M., Tran, T. M., Brock, T. A. & Cunningham, S. A. Cloning of human junctional adhesion molecule 3 (JAM3) and its identification as the JAM2 counter-receptor. J. Biol. Chem. 276, 45826–45832 (2001)

    CAS  Article  PubMed  Google Scholar 

  11. Lui, W. Y., Mruk, D., Lee, W. M. & Cheng, C. Y. Sertoli cell tight junction dynamics: their regulation during spermatogenesis. Biol. Reprod. 68, 1087–1097 (2003)

    CAS  Article  PubMed  Google Scholar 

  12. Kierszenbaum, A. L., Rivkin, E. & Tres, L. L. Acroplaxome, an F-actin-keratin-containing plate, anchors the acrosome to the nucleus during shaping of the spermatid head. Mol. Biol. Cell 14, 4628–4640 (2003)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Ozaki-Kuroda, K. et al. Nectin couples cell–cell adhesion and the actin scaffold at heterotypic testicular junctions. Curr. Biol. 12, 1145–1150 (2002)

    CAS  Article  PubMed  Google Scholar 

  14. Bouchard, M. J. et al. Defects in nuclear and cytoskeletal morphology and mitochondrial localization in spermatozoa of mice lacking nectin-2, a component of cell–cell adherens junctions. Mol. Cell. Biol. 20, 2865–2873 (2000)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  15. Mueller, S., Rosenquist, T. A., Takai, Y., Bronson, R. A. & Wimmer, E. Loss of nectin-2 at Sertoli-spermatid junctions leads to male infertility and correlates with severe spermatozoan head and midpiece malformation, impaired binding to the zona pellucida, and oocyte penetration. Biol. Reprod. 69, 1330–1340 (2003)

    CAS  Article  PubMed  Google Scholar 

  16. Kang-Decker, N., Mantchev, G. T., Juneja, S. C., McNiven, M. A. & van Deursen, J. M. Lack of acrosome formation in Hrb-deficient mice. Science 294, 1531–1533 (2001)

    ADS  CAS  Article  PubMed  Google Scholar 

  17. Etienne-Manneville, S. & Hall, A. Cell polarity: Par6, aPKC and cytoskeletal crosstalk. Curr. Opin. Cell Biol. 15, 67–72 (2003)

    CAS  Article  PubMed  Google Scholar 

  18. Ohno, S. Intercellular junctions and cellular polarity: the PAR-aPKC complex, a conserved core cassette playing fundamental roles in cell polarity. Curr. Opin. Cell Biol. 13, 641–648 (2001)

    CAS  Article  PubMed  Google Scholar 

  19. Erickson, J. W. & Cerione, R. A. Multiple roles for Cdc42 in cell regulation. Curr. Opin. Cell Biol. 13, 153–157 (2001)

    CAS  Article  PubMed  Google Scholar 

  20. Wodarz, A. Establishing cell polarity in development. Nature Cell Biol. 4, E39–E44 (2002)

    CAS  Article  PubMed  Google Scholar 

  21. Ebnet, K. et al. The junctional adhesion molecule (JAM) family members JAM-2 and JAM-3 associate with the cell polarity protein PAR-3: a possible role for JAMs in endothelial cell polarity. J. Cell Sci. 116, 3879–3891 (2003)

    CAS  Article  PubMed  Google Scholar 

  22. Ebnet, K. et al. The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM). EMBO J. 20, 3738–3748 (2001)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  23. Roh, M. H., Fan, S., Liu, C. J. & Margolis, B. The Crumbs3–Pals1 complex participates in the establishment of polarity in mammalian epithelial cells. J. Cell Sci. 116, 2895–2906 (2003)

    CAS  Article  PubMed  Google Scholar 

  24. Straight, S. W. et al. Loss of PALS1 expression leads to tight junction and polarity defects. Mol. Biol. Cell 15, 1981–1990 (2004)

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  25. Nam, S. C. & Choi, K. W. Interaction of Par-6 and Crumbs complexes is essential for photoreceptor morphogenesis in Drosophila. Development 130, 4363–4372 (2003)

    CAS  Article  PubMed  Google Scholar 

  26. Hurd, T. W., Gao, L., Roh, M. H., Macara, I. G. & Margolis, B. Direct interaction of two polarity complexes implicated in epithelial tight junction assembly. Nature Cell Biol. 5, 137–142 (2003)

    CAS  Article  PubMed  Google Scholar 

  27. Hutterer, A., Betschinger, J., Petronczki, M. & Knoblich, J. A. Sequential roles of Cdc42, Par-6, aPKC and Lgl in the establishment of epithelial polarity during Drosophila embryogenesis. Dev. Cell 6, 845–854 (2004)

    CAS  Article  PubMed  Google Scholar 

  28. Lallemand, Y., Luria, V., Haffner-Krausz, R. & Lonai, P. Maternally expressed PGK-Cre transgene as a tool for early and uniform activation of the Cre site-specific recombinase. Transgenic Res. 7, 105–112 (1998)

    CAS  Article  PubMed  Google Scholar 

  29. Izumi, Y. et al. An atypical PKC directly associates and colocalizes at the epithelial tight junction with ASIP, a mammalian homologue of Caenorhabditis elegans polarity protein PAR-3. J. Cell Bi ol. 143, 95–106 (1998)

    CAS  Article  Google Scholar 

  30. Compagni, A., Logan, M., Klein, R. & Adams, R. H. Control of skeletal patterning by ephrinB1–EphB interactions. Dev. Cell 5, 217–230 (2003)

    CAS  Article  PubMed  Google Scholar 

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Acknowledgements

We thank B. Margolis, T. Pawson, E. Peles, A. Suzuki, A. Le Bivic, C. Nobes and P. Parker for reagents and N. Hogg for comments on the manuscript. This work was funded by Cancer Research UK, the EMBO Young Investigator Program (R.H.A.), the Swiss National Science Foundation (M.A.L. and B.A.I.) and Oncosuisse (B.A.I).

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Correspondence to Ralf H. Adams.

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Supplementary information

Supplementary Figure 1

JAM-C gene targeting strategy and verification of the null allele. (PDF 146 kb)

Supplementary Figure 2

Histology showing the lack of mature spermatozoa in the epididymis of JAM-C-deficient mice. (PDF 176 kb)

Supplementary Figure 3

Data confirming the integrity of mutant Sertoli-Sertoli tight junctions. (PDF 214 kb)

Supplementary Figure 4

Additional immunofluorescence data for cell polarity proteins. (PDF 136 kb)

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Gliki, G., Ebnet, K., Aurrand-Lions, M. et al. Spermatid differentiation requires the assembly of a cell polarity complex downstream of junctional adhesion molecule-C. Nature 431, 320–324 (2004). https://doi.org/10.1038/nature02877

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