Research

Nuclear Networking and Cell Function

The Project Leader's Profile

Yoshihiro Yoneda

Yoshihiro Yoneda, M.D., Ph.D., Professor, Biomolecular Dynamics laboratory, Department of Frontier Bioscience, Osaka University and Department of Biochemistry, Osaka University Medical School/Graduate School of Medicine

In 1981, graduated from Osaka University Medical School and obtained his M.D.  In 1985, completed the doctoral course at the Graduate School of Medicine, Osaka University and obtained his Ph.D.  In 1986, appointed as Assistant Professor, in 1991, as Associate Professor and in 1992, as Professor in Institute for Molecular and Cellular Biology, Osaka University.  In 1993, moved to Osaka University Medical School as Professor of Department of Cell Biology and Neuroscience.  Since 2002, he holds the current position.  His main research project is to elucidate the molecular mechanism of nucleocytoplasmic protein transport and its significance to cell functions.

Project Leader
  • Yoshihiro Yoneda, M.D., Ph.D., Professor, Biomolecular Dynamics laboratory, Department of Frontier Bioscience, Osaka University and Department of Biochemistry, Osaka University Medical School/Graduate School of Medicine
Research Members
  • Jun katahira, Associate Professor, Biomolecular Dynamics laboratory, Department of Frontier Bioscience, Osaka University
  • Takeshi Fujiwara, Visiting Associate Professor of the GCOE, Department of Biochemistry, Osaka University Medical School/Graduate School of Medicine
  • Toshihiro Sekimoto, Assistant Professor, Department of Biochemistry, Osaka University Medical School/Graduate School of Medicine
  • Masahiro Oka, Assistant Professor, Biomolecular Dynamics laboratory, Department of Frontier Bioscience, Osaka University
  • Noriko Yasuhara, Visiting Assistant Professor of the GCOE, Department of Biochemistry, Osaka University Medical School/Graduate School of Medicine

Summary

The eukaryotic cell nucleus is rapped by the nuclear envelope, and is physically separated from the cytoplasm. Thousands of nuclear pores penetrate the nuclear envelope, through which many molecules pass between the nucleus and the cytoplasm. Small molecules freely pass the nuclear pore, while larger molecules are selectively transported by specific transport system. There are many kinds of transport receptors participating in the nuclear-cytoplasmic transport, which allow the nuclear-cytoplasmic information exchange by selective and specific transport of the cargo molecules. We have been studying the mechanism of the selective transport of proteins and RNAs, and have revealed the relationship between the transport system and cellular events such as stress response, cell differentiation and cell cycle. From the findings, we now know that the transport systems not only transport the cargo, but the system itself dynamically responds to various extracellular and intracellular environmental changes to support the cellular events. For example, certain protein transport receptors accumulate in the nucleus under stress condition. It possibly enhances specific transport pathway which enables stress responding factors to efficiently enter the nucleus. Furthermore, during stem cell differentiation, certain receptors for protein transport change their expression levels to facilitate the import of appropriate transcription factors. These changes in the receptor expression levels are indispensible for cell differentiation, and we are able to induce differentiation just by mimicking the changes. Thus, the nuclear-cytoplasmic transport plays a significant role in cell fate determination. Additionally, it is reported that the nuclear pore also responds to environmental changes during cellular events, by regulating the transport through interaction with the transport receptors, and by changing its shape, distribution or components.
Although some part of significant relationship between the nuclear-cytoplasmic transport system and the cellular events are revealed, there are many things left to be elucidated. The transport system may dynamically change to participate in cellular events such as virus infection, apoptosis, senescence, and tissue formation. In the program of GCOE, we will investigate when and how the transport system change, and how the system change steers cell functions, to elucidate the cellular events from the viewpoint of the nuclear-cytoplasmic information exchanging network.

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Some of Recent Papers

  1. Kamei, Y., Suzuki, M., Watanabe, K., Fujimori, K., Kawasaki, T., Deguchi, T., Yoneda, Y., Todo, T., Takagi, S., Funatsu, T. and Yuba, S.  Infrared laser-mediated gene induction in targeted single cells in vivo.  Nat Methods,  6(1): 79-81 (2009)
  2. Katahira J., Inoue H., Hurt E. and Yoneda Y.  Adaptor Aly and co-adaptor Thoc5 function in the Tap-p15-mediated nuclear export of HSP70 mRNA. EMBO J., 28(5): 556-567 (2009)
  3. Okada, C., Yamashita, E., Lee, S. J., Shibata, S., Katahira, J., Nakagawa, A., Yoneda, Y. and Tsukihara, T.  A high-resolution structure of the pre-microRNA nuclear export machinery.  Science,  326(5957): 1275-1279 (2009)
  4. Otsuka, S., Iwasaka, S., Yoneda, Y., Takeyasu, K. and Yoshimura, S. H.  Individual binding pockets of importin β for FG-nucleoporins have different binding properties and different sensitivities to RanGTP. Proc Natl Acad Sci USA, 105(42): 16101-16106 (2008)
  5. Yudin D., Hanz S., Yoo S., Iavnilovitch E., Willis D., Gradus T., Segal-Ruder Y., Ben-Yaakov K., Hieda M., Yoneda Y., Twiss J. L. and Fainzilber M.  Localized regulation of axonal RanGTPase controls retrograde injury signaling in peripheral nerve. Neuron, 59(2): 241-252 (2008)