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:

Role of the PAR-3–KIF3 complex in the establishment of neuronal polarity

Nature Cell Biology volume 6, pages 328–334 (2004)Cite this article

Abstract

Neurons polarize to form elaborate multiple dendrites and one long axon. The establishment and maintenance of axon/dendrite polarity are fundamentally important for neurons. Recent studies have demonstrated that the polarity complex PAR-3–PAR-6–atypical protein kinase C (aPKC) is involved in polarity determination in many tissues and cells. The function of the PAR-3–PAR-6–aPKC protein complex depends on its subcellular localization in polarized cells. PAR-3 accumulates at the tip of growing axons in cultured rat hippocampal neurons, but the molecular mechanism of this localization remains unknown. Here we identify a direct interaction between PAR-3 and KIF3A, a plus-end-directed microtubule motor protein, and show that aPKC can associate with KIF3A through its interaction with PAR-3. The expression of dominant-negative PAR-3 and KIF3A fragments that disrupt PAR-3–KIF3A binding inhibited the accumulation of PAR-3 and aPKC at the tip of the neurites and abolished neuronal polarity. These results suggest that PAR-3 is transported to the distal tip of the axon by KIF3A and that the proper localization of PAR-3 is required to establish neuronal polarity.

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: Interaction of PAR-3 with KIF3 in vitro.
Figure 2: Interaction of the PAR-3–aPKC complex with KIF3.
Figure 3: Localization of PAR-3 and KIF3 in cultured rat hippocampal neurons.
Figure 4: De-localization of PAR-3 and aPKC from the tip of the neurites.
Figure 5: Effect of dominant-negative PAR-3 and KIF3A fragments on neuronal polarity.

Similar content being viewed by others

References

  1. Craig, A.M. & Banker, G. Neuronal polarity. Annu. Rev. Neurosci. 17, 267–310 (1994).

    Article  CAS  Google Scholar 

  2. Dotti, C.G., Sullivan, C.A. & Banker, G.A. The establishment of polarity by hippocampal neurons in culture. J. Neurosci. 8, 1454–1468 (1988).

    Article  CAS  Google Scholar 

  3. Bradke, F. & Dotti, C.G. Establishment of neuronal polarity: lessons from cultured hippocampal neurons. Curr. Opin. Neurobiol. 10, 574–581 (2000).

    Article  CAS  Google Scholar 

  4. Fukata, Y., Kimura, T. & Kaibuchi, K. Axon specification in hippocampal neurons. Neurosci. Res. 43, 305–315 (2002).

    Article  CAS  Google Scholar 

  5. Kemphues, K. PARsing embryonic polarity. Cell 101, 345–348 (2000).

    Article  CAS  Google Scholar 

  6. Jan, Y.N. & Jan, L.Y. Asymmetric cell division in the Drosophila nervous system. Nature Rev. Neurosci. 2, 772–779 (2001).

    Article  CAS  Google Scholar 

  7. 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  Google Scholar 

  8. Shi, S.H., Jan, L.Y. & Jan, Y.N. Hippocampal neuronal polarity specified by spatially localized mPar-3–mPar-6 and PI 3-kinase activity. Cell 112, 63–75 (2003).

    Article  CAS  Google Scholar 

  9. Lin, D. et al. A mammalian PAR-3–PAR-6 complex implicated in Cdc42/Rac1 and aPKC signalling and cell polarity. Nature Cell Biol. 2, 540–547 (2000).

    Article  CAS  PubMed  Google Scholar 

  10. Kondo, S. et al. KIF3A is a new microtubule-based anterograde motor in the nerve axon. J. Cell Biol. 125, 1095–1107 (1994).

    Article  CAS  Google Scholar 

  11. Yamazaki, H., Nakata, T., Okada, Y. & Hirokawa, N. KIF3A/B: a heterodimeric kinesin superfamily protein that works as a microtubule plus end-directed motor for membrane organelle transport. J. Cell Biol. 130, 1387–1399 (1995).

    Article  CAS  Google Scholar 

  12. Yang, Z. & Goldstein, L.S. Characterization of the KIF3C neural kinesin-like motor from mouse. Mol. Biol. Cell 9, 249–261 (1998).

    Article  CAS  PubMed  Google Scholar 

  13. Muresan, V. et al. KIF3C and KIF3A form a novel neuronal heteromeric kinesin that associates with membrane vesicles. Mol. Biol. Cell 9, 637–652 (1998).

    Article  CAS  PubMed  Google Scholar 

  14. Goldstein, L.S. & Yang, Z. Microtubule-based transport systems in neurons: the roles of kinesins and dyneins. Annu. Rev. Neurosci. 23, 39–71 (2000).

    Article  CAS  Google Scholar 

  15. Lupas, A., VanDyke, M. & Stock, J. Predicting coiled coils from protein sequences. Science 252, 1162–1164 (1991).

    Article  CAS  Google Scholar 

  16. Yamazaki, H., Nakata, T., Okada, Y. & Hirokawa, N. Cloning and characterization of KAP3: a novel kinesin superfamily-associated protein of KIF3A/3B. Proc. Natl Acad. Sci. USA 93, 8443–8448 (1996).

    Article  CAS  Google Scholar 

  17. Takeda, S. et al. Kinesin superfamily protein 3 (KIF3) motor transports fodrin-associating vesicles important for neurite building. J. Cell Biol. 148, 1255–1265 (2000).

    Article  CAS  PubMed  Google Scholar 

  18. Jimbo, T. et al. Identification of a link between the tumour suppressor APC and the kinesin superfamily. Nature Cell Biol. 4, 323–327 (2002).

    Article  CAS  Google Scholar 

  19. Akimoto, K. et al. EGF or PDGF receptors activate atypical PKCλ through phosphatidylinositol 3-kinase. EMBO J. 15, 788–798 (1996).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  21. Suzuki, A. et al. Atypical protein kinase C is involved in the evolutionarily conserved par protein complex and plays a critical role in establishing epithelia-specific junctional structures. J. Cell Biol. 152, 1183–1196 (2001).

    Article  CAS  PubMed  Google Scholar 

  22. Inagaki, N. et al. CRMP-2 induces axons in cultured hippocampal neurons. Nature Neurosci. 4, 781–782 (2001).

    Article  CAS  Google Scholar 

  23. Fukata, Y. et al. CRMP-2 binds to tubulin heterodimers to promote microtubule assembly. Nature Cell Biol. 4, 583–591 (2002).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank M. Fukata, M. Nakagawa and J. Noritake for discussion; M. Yoshizaki and K. Fujii for preparing materials and technical assistance; T. Ishii for secretarial assistance. This research was supported by Grants-in-Aid for Scientific Research and Grant-in-Aid for Creative Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan and the Organization for Pharmaceutical Safety and Research.

Author information

Author notes

  1. Takashi Nishimura and Katsuhiro Kato: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cell Pharmacology, Graduate School of Medicine, Nagoya University, 65 Tsurumai, Showa, Nagoya, 466-8550, Aichi, Japan

    Takashi Nishimura, Katsuhiro Kato, Tomoya Yamaguchi, Yuko Fukata & Kozo Kaibuchi

  2. Department of Molecular Biology, Yokohama City University School of Medicine, Fuku-ura 3-9, Kanazawa-ku, Yokohama, 236-0004, Japan

    Shigeo Ohno

Authors
  1. Takashi Nishimura
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Katsuhiro Kato
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tomoya Yamaguchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yuko Fukata
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Shigeo Ohno
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Kozo Kaibuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kozo Kaibuchi.

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

Nishimura, T., Kato, K., Yamaguchi, T. et al. Role of the PAR-3–KIF3 complex in the establishment of neuronal polarity. Nat Cell Biol 6, 328–334 (2004). https://doi.org/10.1038/ncb1118

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ncb1118

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