2001 - Ph.D. Pharmacology, Juntendo Univ. Sch. of Med., Tokyo, Japan
1992 - M.S. Physiology, Chiba Univ., Chiba, Japan
1990 - B.S. Biology, Chiba Univ., Chiba, Japan
Characterization of motor proteins and the related proteins. Mechanisms underlying regulation of smooth muscle.
- Characterization of unconventional myosins (VA, VI, VIIA, X, XI, etc.)
- Identification and characterization of smooth muscle myosin phosphatase phosphatase (SMMPP)
Motor proteins are a series of molecular motors that move along a suitable track. An example of motor proteins is “myosin” that is well-known as muscle motor protein in animals. Recent studies have revealed that myosins play critical roles in diverse cellular processes such as muscle contraction, cytokinesis, cell motility, endo- or exocytosis, maintenance of cell shape, active transport of proteins, and membrane trafficking, etc. Defects of muscular myosins cause human congenital myopathy and hypertrophic cardiomyopathy, whereas defects in several unconventional myosins are predictably involved in human deafness/blindness syndromes. The current project will study how motor proteins work in cells, and how the deficits lead to a number of human genetic disorders.
One of our research interests is single molecule measurements of myosins or the related proteins using nano-spectroscopy. An outstanding question is how myosins work at the specific locations, and how the structure of myosins and the related proteins affect their functions. We specialize in applying high precision measurements using a Total Internal Reflection Fluorescence (TIRF) microscope to answer these and other questions.
Another interest is to clarify the mechanisms underlying the regulation of smooth muscle. Smooth muscle myosin is regulated by phosphorylation and dephosphorylation of myosin light chain (MLC), and the phosphorylation level is determined by the enzyme activities of MLC kinase and MLC phosphatase. We are particularly focused on the mechanisms how MLC phosphatase is regulated in smooth muscle.
Our researches include various biochemical techniques such as enzyme activity measurements, protein expression by E. coli or baculovirus expression system, protein purification using various column chromatography systems including FPLC and HPLC, kinetic measurements using stopped-flow apparatus, in vitro single or multi-molecule motility measurements using fluorescence microscope, etc.
Kwon, T.J., Oh, S.K., Park, H.J., Sato, O., Venselaar, H., Choi, S.Y., Kim, S., Lee, K.Y., Bok, J., Lee, S.H., Vriend, G., Ikebe, M., Kim, U.K., Choi, J.Y. (2014) The effect of novel mutations on the structure and enzymatic activity of unconventional myosins associated with autosomal dominant non-syndromic hearing loss. Open Biol. In press.
Kakizawa, S., Yamazawa, T.,Chen, Y.,Ito, A., Saito, N., Murayama, T., Kurebayashi, N., Sato, O., Sakurai, T., Oyamada, H., Oguchi, K., Watanabe, M., Mori, M., Takeshima, H., Iino, M. (2011) Nitric oxide-induced calcium release via ryanodine receptors regulates neuronal function. EMBO Journal, 31, 417-428.
Umeki, N., Jung, H-S., Sakai, T., Sato, O., Ikebe, R., Ikebe, M. (2011) Phospholipid-dependent regulation of the motor activity of myosin X. Nature Struct. Mol. Biol., 18, 783-788
Ressmeyer, A.R., Bai, Y., Delmotte, P., Uy, K. F., Thistlethwaite, P., Fraire, A. Sato, O., Ikebe, M.,Sanderson, M. J. (2010) Human airway contraction and formoterol-induced relaxation is determined by Ca2+ oscillations and Ca2+ sensitivity. Am. J. Respir. Cell Mol. Biol. 43, 179-191.
Sun, Y., Sato, O., Ruhnow, F., Arsenault, M.E., Ikebe, M., Goldman, Y.E. (2010) Single-molecule stepping and structural dynamics of myosin X. Nat. Struct. Mol. Biol. 17, 485-491.
Komaba, S., Watanabe, S., Umeki, N., Sato, O., Ikebe, M. (2010) Effect of phosphorylation in the motor domain of human myosin IIIA on its ATP hydrolysis cycle. Biochemistry 49, 3695-3702.