Laboratory for Cell Polarity Regulation

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.

Research Subjects

• Regulatory mechanism for polar transport
• High resolution live imaging of the cytoskeleton and intracellular transport
• High resolution imaging of the cytoskeleton and intracellular transport in animals and enhancement of gene manipulation techniques in animals.

Publications

1. Yajima, H., et al.:
   "Conformational changes in tubulin in GMPCPP and GDP-taxol Microtubules observed by cryo electron microscopy."
   J Cell Biol., 198: 315-322, 2012
2. 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
3. Hirokawa, N., Tanaka, Y., Okada, Y.:
   "The mechanisms of kinesin motor motility: lessons from the monomeric motor KIF1A."
   Nature Reviews Molecular Cell Biology 10: 877-884, 2009
4. Okada, Y., Hirokawa, N.:
   "Observation of Nodal Cilia Movement and Measurement of Nodal Flow."
   Methods in Cell Biology, 91: 265-285, 2009
5. Hirokawa, N., Okada, Y., Tanaka, Y.:
   "Fluid Dynamic Mechanism Responsible for Breaking the Left-Right Symmetry of the Human Body: The Nodal Flow."
   Annual Review of Fluid Mechanics 41: 53-72, 2009
6. Nitta, R., Okada, Y., Hirokawa, N.:
   "Structural model for strain-dependent microtubule activation of Mg-ADP release from kinesin."
   Nature Structural and Molecular Biology 15: 1067-1075, 2008
7. Hirokawa, N., Tanaka, Y., Okada, Y., Takeda, S.:
   "Nodal flow and the generation of left-right asymmetry."
   Cell 125: 33-45, 2006
8. Tanaka, Y., Okada, Y., Hirokawa, N.:
   "FGF-induced vesicular release of Sonic hedgehog and retinoic acid in leftward nodal flow is critical for left-right determination."
   Nature. 435:172-7. 2005
9. Okada, Y., Takeda, S., Tanaka, Y., Izpisúa-Belmonte, J.C., Hirokawa, N.:
   "Mechanism of nodal flow: a conserved symmetry breaking event in left-right axis determination."
   Cell. 121:633-44. 2005
10. Nishinari, K., Okada, Y., Schadschneider, A., Chowdhury, D.:
    "Intracellular transport of single-headed molecular motors KIF1A."
    Phys Rev Lett. 95:118101. 2005