Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

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

Nature volume 431, pages 320–324 (2004)Cite this article

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

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.

Similar content being viewed by others

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)

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  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)

    Article  CAS  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)

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  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)

    Article  CAS  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)

    Article  CAS  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)

    Article  CAS  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)

    Article  CAS  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)

    Article  CAS  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)

    Article  CAS  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)

    Article  CAS  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)

    Article  CAS  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)

    Article  ADS  CAS  PubMed  Google Scholar 

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

    Article  CAS  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)

    Article  CAS  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)

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  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)

    Article  CAS  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)

    Article  CAS  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)

    Article  CAS  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)

    Article  CAS  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)

    Article  CAS  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)

    Article  CAS  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)

    Article  CAS  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)

    Article  CAS  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)

    Article  CAS  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)

    Article  CAS  PubMed  Google Scholar 

Download references

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).

Author information

Authors and Affiliations

  1. Vascular Development Laboratory, Cancer Research UK London Research Institute, WC2A 3PX, London, UK

    Georgia Gliki & Ralf H. Adams

  2. Institute of Cell Biology, ZMBE, University Hospital Muenster, D-48149, Muenster, Germany

    Klaus Ebnet

  3. Department of Pathology, University of Geneva, CMU, CH-1211, Geneva, Switzerland

    Michel Aurrand-Lions & Beat A. Imhof

Authors
  1. Georgia Gliki
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Klaus Ebnet
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michel Aurrand-Lions
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Beat A. Imhof
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ralf H. Adams
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ralf H. Adams.

Ethics declarations

Competing interests

The authors declare that they have no competing financial interests.

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)

Rights and permissions

Reprints and permissions

About this article

Cite this article

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

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nature02877

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing