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The KIF3 motor transports N-cadherin and organizes the developing neuroepithelium

Nature Cell Biology volume 7, pages 474–482 (2005)Cite this article

A Corrigendum to this article was published on 01 June 2005

Abstract

In the developing brain, the organization of the neuroepithelium is maintained by a critical balance between proliferation and cell–cell adhesion of neural progenitor cells. The molecular mechanisms that underlie this are still largely unknown. Here, through analysis of a conditional knockout mouse for the Kap3 gene, we show that post-Golgi transport of N-cadherin by the KIF3 molecular motor complex is crucial for maintaining this balance. N-cadherin and β-catenin associate with the KIF3 complex by co-immunoprecipitation, and colocalize with KIF3 in cells. Furthermore, in KAP3-deficient cells, the subcellular localization of N-cadherin was disrupted. Taken together, these results suggest a potential tumour-suppressing activity for this molecular motor.

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Figure 1: Mosaic deletion of KAP3 leads to malignant transformation of neuroepithelium.
Figure 2: Enlargement of the neural progenitor pool the in conditional knockout mouse.
Figure 3: Altered subcellular localization of N-cadherin in the conditional knockout mouse brain.
Figure 4: Decreased level of cell aggregation activity in KAP3-deficient MEFs (knockout, KO).
Figure 5: Altered subcellular localization of N-cadherin in KAP3-deficient MEFs.
Figure 6: Impaired post-Golgi transport of N-cadherin–GFP in knockout MEFs.
Figure 7: The KIF3 heterotrimeric motor is associated with N-cadherin and β-catenin.
Figure 8: Time-lapse images of KAP3A–YFP and N-cadherin–CFP signals in A431D cells.

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Acknowledgements

We thank J. Miyazaki (Osaka University) for CAG-Cre mouse, M. Takeichi (RIKEN CDB, Kobe, Japan) for N-cadherin cDNA, M. J. Wheelock (Eppley Institute, Nebraska) for A431D cell line, T. Yagi (Osaka University) for pCre-Pac plasmid, and N. Osumi (Tohoku University) and Y. Gotoh (Tokyo University) for valuable suggestions on early brain development. We also thank H. Sato, H. Fukuda, M. Sugaya-Otsuka, N. Onouchi and T. Aizawa for technical assistance, and Y. Kanai, Y. Noda, Y. Okada, S. Takeda, M. Kawagishi, S. Niwa and other members of the Hirokawa laboratory for valuable discussions. This work was supported by a Center of Excellence grant from the Ministry of Education, Culture, Sports, Science and Technology of Japan to N. H., and postdoctoral fellowships from Japanese Society for the Promotion of Science to J. T and T. R.

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Author notes

  1. Motoyuki Hirasawa

    Present address: Department of Neurology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

  2. Junlin Teng and Tatemitsu Rai: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Junlin Teng, Tatemitsu Rai, Yosuke Tanaka, Yosuke Takei, Takao Nakata & Nobutaka Hirokawa

  2. Functional Genomics Section, Craniofacial Developmental Biology and Regeneration Branch, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, 20892-4326, MD, USA

    Motoyuki Hirasawa & Ashok B. Kulkarni

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Teng, J., Rai, T., Tanaka, Y. et al. The KIF3 motor transports N-cadherin and organizes the developing neuroepithelium. Nat Cell Biol 7, 474–482 (2005). https://doi.org/10.1038/ncb1249

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