Team Leader

Yasushi Okada (M.D., Ph.D.)

Our work has focused on in vitro studies of the single molecule motors. We have combined single molecule imaging, gene manipulation, and structural biology techniques to study the mechanisms responsible for such function. Currently we are attempting to extend our methods to observe such function intracellularly to confirm the regulating mechanism(s). Motor proteins transport a variety of elements inside the cell. In fact, so important is this transport that it is not an exaggeration to describe it as the lifeline of a cell. When a motor malfunctions, the cell’s internal navigation system becomes disabled so that transport is compromised. We are studying the navigation system by directly observing transportation using new imaging techniques and the motor protein kinesin KIF5, a key regulator for axonal development, as our model. Despite neurons extending a large number of projections, only one becomes an axon. Recently, we have discovered that the structures of the microtubules on which kinesins travel in dendrites and the axon are different. KIF5 can recognize the structural difference between these microtubules and therefore be used to determine which neural projections become the axon and which become dendrites.

Selected Publications

• Takai, A., Nakano, M., Saito, K., Haruno, R., Watanabe, T. M., Ohyanagi, T., et al.
  "Expanded palette of Nano-lanterns for real-time multicolor luminescence imaging"
  Proc. Natl. Acad. Sci. U.S.A. 112, 4352-4356 (2015) doi:10.1073/pnas.1418468112
  
• Hayashi, S. & Okada, Y.
  "Ultrafast superresolution fluorescence imaging with spinning disk confocal microscope optics "
  Mol. Biol. Cell 26, 1743-1751 (2015) doi:10.1091/mbc.E14-08-1287
  
• Okada, Y. & Nakagawa, S.
  "Super-resolution imaging of nuclear bodies by STED microscopy"
  Methods Mol. Biol. 1262, 21-35 (2015)
  
• Uno, S., Kamiya, M., Yoshihara, T., Sugawara, K., Okabe, K., Tarhan, M. C., et al.
  "A spontaneously blinking fluorophore based on intramolecular spirocyclization for live-cell super-resolution imaging"
  Nat. Chem. 6, 681-689 (2014) doi:10.1038/nchem.2002
  
• Yajima, H., Ogura, T., Nitta, R., Okada, Y., Sato, C. & Hirokawa, N.
  "Conformational changes in tubulin in GMPCPP and GDP-taxol microtubules observed by cryoelectron microscopy "
  J. Cell Biol. 198, 315-322 (2012) doi:10.1083/jcb.201201161
  
• Hirokawa, N., Tanaka, Y. & Okada, Y.
  "Cilia, KIF3 molecular motor and nodal flow "
  Curr. Opin. Cell Biol. 24, 31-39 (2012) doi:10.1016/j.ceb.2012.01.002
  
• Nakata, T., Niwa, S., Okada, Y., Perez, F. & Hirokawa, N.
  "Preferential binding of a kinesin-1 motor to GTP-tubulin-rich microtubules underlies polarized vesicle transport "
  J. Cell Biol. 194, 245-255 (2011) doi:10.1083/jcb.201104034
  
• Hirokawa, N., Nitta, R. & Okada, Y.
  "The mechanisms of kinesin motor motility: lessons from the monomeric motor KIF1A "
  Nat. Rev. Mol. Cell Biol. 10, 877-884 (2009) doi:10.1038/nrm2807