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:

An NDPase links ADAM protease glycosylation with organ morphogenesis in C. elegans

Nature Cell Biology volume 6, pages 31–37 (2004)Cite this article

Abstract

In the nematode Caenorhabditis elegans, the gonad acquires two U-shaped arms through the directed migration of its distal tip cells (DTCs), which are located at the tip of the growing gonad arms1. A member of the ADAM (a disintegrin and metalloprotease) family, MIG-17, regulates directional migration of DTCs: MIG-17 is synthesized and secreted from the muscle cells of the body wall, and diffuses to the gonad where it is required for DTC migration2. The mig-23 mutation causes defective migration of DTCs and interacts genetically with mig-17. Here, we report that mig-23 encodes a membrane-bound nucleoside diphosphatase (NDPase) required for glycosylation and proper localization of MIG-17. Our findings indicate that an NDPase affects organ morphogenesis through glycosylation of the MIG-17 ADAM protease.

Access through your institution
Buy or subscribe

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

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

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

Figure 1: Wild-type and mutant gonad morphology.
Figure 2: Structure and activity of MIG-23.
Figure 3: Glycan modification of MIG-17.
Figure 4: Expression of mig-23 and mig-17.

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. Kimble, J.E. & White, J.G. On the control of germ cell development in C. elegans. Dev. Biol. 81, 208–219 (1981).

    Article  CAS  PubMed  Google Scholar 

  2. Nishiwaki, K., Hisamoto, N. & Matsumoto, K. A metalloprotease disintegrin that controls cell migration in Caenorhabditis elegans. Science 288, 2205–2208 (2000).

    Article  CAS  PubMed  Google Scholar 

  3. Hedgecock, E.M., Culotti, J.G., Hall, D.H. & Stern, B.D. Genetics of cell and axon migrations in Caenorhabditis elegans. Development 100, 365–382 (1987).

    CAS  PubMed  Google Scholar 

  4. Blelloch, R. & Kimble, J. Control of organ shape by a secreted metalloprotease in the nematode Caenorhabditis elegans. Nature 399, 586–590 (1999).

    Article  CAS  PubMed  Google Scholar 

  5. Komoszynski, M. & Wojtczak, A. Apyrases (ATP diphosphohydrolases, EC 3.6.1.5): function and relationship to ATPases. Biochim. Biophys. Acta 1310, 233–241 (1996).

    Article  PubMed  Google Scholar 

  6. Wang, T.F. & Guidotti, G. Golgi localization and functional expression of human uridine diphosphatase. J. Biol. Chem. 273, 11392–11399 (1998).

    Article  CAS  PubMed  Google Scholar 

  7. Gao, X.-D., Kaigorodov, V. & Jigami, Y. YND1, a homologue of GDA1, encodes membrane-bound apyrase required for Golgi N- and O-glycosylation in Saccharomyces cerevisiae. J. Biol. Chem. 274, 21450–21456 (1999).

    Article  CAS  PubMed  Google Scholar 

  8. Okkema, P.G., Harrison, S.W., Plunger, V., Aryana, A. & Fire, A. Sequence requirements for myosin gene-expression and regulation in Caenorhabditis elegans. Genetics 135, 385–404 (1993).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Hwang, H.-Y., Olson, S.K., Esko, J.D. & Horvitz, H.R. Caenorhabditis elegans early embryogenesis and vulval morphogenesis require chondroitin biosynthesis. Nature 423, 439–443 (2003).

    Article  CAS  PubMed  Google Scholar 

  10. Goto, S. et al. UDP-sugar transporter implicated in glycosylation and processing of Notch. Nature Cell Biol. 3, 816–822 (2001).

    Article  CAS  PubMed  Google Scholar 

  11. Gilleard, J.S., Barry, J.D. & Johnstone, I.L. cis regulatory requirements for hypodermal cell-specific expression of the Caenorhabditis elegans cuticle collagen gene dpy-7. Mol. Cell. Biol. 17, 2301–2311 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Hirschberg, C.B. in Transporter of Nucleotides and Nucleotide Derivatives in the Endoplasmic Reticulum and Golgi Apparatus (eds Clapham, D.E. & Ehrlich, B.E.) 105–120 (Rockefeller University Press, New York, 1996).

    Google Scholar 

  13. Selva, E.M. et al. Dual role of the fringe connection gene in both heparan sulfate and fringe-dependent signalling events. Nature Cell Biol. 3, 3809–3815 (2001).

    Article  Google Scholar 

  14. Iino, M., Foster, D.C. & Kisiel, W. Functional consequences of mutations in Ser-52 and Ser-60 in human blood coagulation factor VII. Arch. Biochem. Biophys. 352, 182–192 (1998).

    Article  CAS  PubMed  Google Scholar 

  15. Nishiwaki, K. Mutations affecting symmetrical migration of distal tip cells in Caenorhabditis elegans. Genetics 152, 985–997 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Brenner, S. The genetics of Caenorhabditis elegans. Genetics 77, 71–94 (1974).

    CAS  PubMed  PubMed Central  Google Scholar 

  17. Ketting, R.F., Haverkamp, T.H.A., van Luenen, H.G.A.M. & Plasterk, R.H.A. mut-7 of C. elegans, required for transposon silencing and RNA interference, is a homolog of Werner syndrome helicase and RNaseD. Cell 99, 133–141 (1999).

    Article  CAS  PubMed  Google Scholar 

  18. Mello, C.C., Kramer, J.M., Stinchcomb, D. & Ambros, V. Efficient gene transfer in C. elegans: extrachromosomal maintenance and integration of transforming sequences. EMBO J. 10, 3959–3970 (1991).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Yochem, J., Gu, T. & Han, M. A new marker for mosaic analysis in Caenorhabditis elegans indicates a fusion between hpy6 and hyp7, two major components of hypodermis. Genetics 149, 1323–1334 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Abeijon, C., Orlean, P., Robbins, P.W. & Hirschberg, C.B. Topography of glycosylation in yeast: characterization of GDP mannose transport and lumenal guanosine diphosphatase activities in Golgi-like vesicles. Proc. Natl Acad. Sci. USA 86, 6935–6939(1989).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Graham, P.L. et al. Type IV collagen is detectable in most, but not all, basement membranes of Caenorhabditis elegans and assembles on tissues that do not express it. J. Cell Biol. 137, 1171–1183 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank A. Coulson, A. Fire, Y. Kohara, T. Stiernagle and the Caenorhabditis Genetics Center for materials; and M. Lamphier and A. Spence for critical reading of the manuscript. This work was supported by special grants for PRESTO (K. N.), CREST and Advanced Research on Cancer from the Ministry of Education, Culture and Science of Japan (K. M.).

Author information

Authors and Affiliations

  1. RIKEN Center for Developmental Biology and PRESTO, Japan Science and Technology Corporation, Chuo-ku, Kobe, 650-0047, Japan

    Kiyoji Nishiwaki & Yukihiko Kubota

  2. Research Center for Glycoscience, National Institute of Advanced Industrial Science and Technology, AIST Central 6, Tsukuba, 305-8566, Japan

    Yuko Chigira, Samir Kumar Roy & Yoshifumi Jigami

  3. Department of Molecular Biology, Graduate school of Science, Institute for Advanced Research, Nagoya University, and CREST, Japan Science and Technology Corporation, Chikusa-ku, Nagoya, 464-8602, Japan

    Maho Suzuki, Naoki Hisamoto & Kunihiro Matsumoto

  4. Department of Molecular and Medical Genetics, University of Toronto, Toronto, M5S 1A8, Ontario, Canada

    Mara Schvarzstein

Authors
  1. Kiyoji Nishiwaki
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Yukihiko Kubota
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Yuko Chigira
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Samir Kumar Roy
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Maho Suzuki
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Mara Schvarzstein
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Yoshifumi Jigami
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Naoki Hisamoto
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Kunihiro Matsumoto
    View author publications

    You can also search for this author inPubMed Google Scholar

Corresponding author

Correspondence to Kiyoji Nishiwaki.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nishiwaki, K., Kubota, Y., Chigira, Y. et al. An NDPase links ADAM protease glycosylation with organ morphogenesis in C. elegans. Nat Cell Biol 6, 31–37 (2004). https://doi.org/10.1038/ncb1079

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb1079

This article is cited by

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