Higuchi LAB

               Biophysics on biomolecular dynamics

Department of Physics, School of Science, The University of Tokyo



Hideo Higuchi   Motoshi Kaya  
Sayaka Kita   Seine Shintani  

Hideo Higuchi

  1. Hirota Y., A. Meunier, S.Huang, T. Shimozawa, O.Yamada, Y.S Kida, M. Inoue, T. Ito, H. Kato, M. Sakaguchi, T. Sunabori, M. Nakaya, S. Nonaka, T. Ogura, H. Higuchi, H. Okano, N.Spassky, and *K. Sawamoto. Planar polarity of multiciliated ependymal cells involves the anterior mi-gration of basal bodies regulated by non-muscle myosin II. Development, In press (2010)
  2. Kaya M. and *H. Higuchi. Non-linear elasticity and an 8 nm working stroke of single myosin molecules in myofilaments. Science, 329, 686-689 (2010)
  3. Fujita H, H. Hatakeyama, TM. Watanabe, M. Sato, H. Higuchi and * M. Kanzaki. Identification of Three Distinct Functional Sites of Insulin-mediated GLUT4 Trafficking in Adipocytes Using Quantitative Single Molecule Imaging. Mol. Biol. Cell, 21, 2721-2731 (2010)
  4. Watanabe TM, H. Tokuo, K. Gonda, H. Higuchi and * M. Ikebe. Myosin-X induces filopodia by multiple elongation mechanism. J. Biol. Chem. 285, 19605-14 (2010)
  5. Gonda K., T M. Watanabe N.Ohuchi, and *H. Higuchi. In Vivo Nano-imaging of Membrane Dynamics in Metastatic Tumor Cells Using Quantum Dots. J. Biol. Chem. 285,2750-2757 (2010)
  6. Kawai M., H. Higuchi, M. Takeda, Y. Kobayashi and N. Ohuchi. Dynamics of different-sized solid-state nanocrystals as tracers for a drug-delivery system in the interstitium of a human tu-mor xenograf. Breast Cancer Research, 11: R43 (2009) (Open access publication)
  7. Furuta A., T. Yagi, H. Yanagisawa, H. Higuchi, and *R. Kamiya. Systematic comparison of In vitro motile properties between chlamydomonas wild-type and mutant outer arm dyneins each lacking one of the three heavy chain. J. Biol. Chem. 284, 5927-5935 (2009).
  8. Yoo J., T. Kambara, K. Gonda, and *H. Higuchi. Intracellular imaging of targeted proteins labeled with Quantum Dots. Exp Cell Res. 314, 3563-3569 (2008)
  9. Sazaki, G., M.Okada, T. Matsui, T. Watanabe, H. Higuchi, K. Tsukamoto and K. Nakajima. Single-Molecule Visualization of Diffusion at the Solution-Crystal Interface. Crtstal Growth and Design. 8, 2024-2031 (2008)
  10. Watanabe S., T.M. Watanabe, O. Sato, J. Awata, K. Homma, N. Umeki, H. Higuchi, R. Ikebe, and *M. Ikebe. Human Myosin Vc is a Low Duty Ratio Nonprocessive Motor. J. Biol. Chem. 283, 10581-10592 (2008)
  11. Watanabe, T.M., T. Sato, K. Gonda and *H. Higuchi. Three-dimensional nanometry of vesicle transport in a living cell using dual-focus imaging optics. Biochem. Biophys. Res. Comm. 359 1-7 (2007)
  12. Watanabe, T.M. and *H. Higuchi. Stepwise Movements in Vesicle Transport of HER2 by Motor Proteins in Living Cells. Biophysical J. 92, 4109-4120, (2007)
  13. Tada, H., *H. Higuchi, T.M. Watanabe, and N. Ohuchi. In vivo Real-time Tracking of Single Quantum Dots Conjugated with Monoclonal Anti-HER2 Antibody in Tumors of Mice. Cancer Res. 67, 1138-1144, (2007).
  14. Li-Shishido, S., T.M. Watanabe, H. Tada, *H. Higuchi and N. Ohuchi. Reduction in nonfluorescence state of quantum dots on an immunofluorescence staining. Biochem. Biophys. Res. Comm. 351, 7-13, (2006).
  15. Toba, S., T.M. Watanabe, L-Y Okimoto, Y.Y. Toyoshima and *H. Higuchi. Overlapping hand-over-hand mechanism of single molecular motility of cytoplasmic dynein. Proc. Natl. Acad. Sci. USA. 103, 5741-5745, (2006).
  16. Nguyen, A.H., V.T. Nguyen, Y. Kamio and *H. Higuchi. Single-Molecule Visualization of Environment-Sensitive Fluorophores Inserted into cell membranes by Staphylococcal gamma-hemolysin. Biochemistry 45, 2570-2576, (2006).
  17. Nguyen, H., and *H. Higuchi. Motility of myosin V regulated by the dissociation of single calmodulin. Nature Struct. Mol. Biol. 12, 127-132, (2005).
  18. Monma, N., V.T. Nguyen, J. Kaneko, H. Higuchi and *Y. Kamio. Essential Residues, W177 and R198, of LukF for Phosphatidylcholine-Binding and Pore-Formation by Staphylococcal gamma-Hemolysin on Human Erythrocyte Membranes. J. Biochem (Tokyo). 136, 427-431, (2004).
  19. Uemura, S., H. Higuchi, A.O. Olivares, E.M. De La Cruz and *S. Ishiwata. Mechanochemical coupling of two substeps in a single myosin V motor. Nature Struct. Mol. Biol. 11, 877-883,(2004).
  20. Higuchi, H., C.E. Bronner, H.W. Park and *S.A. Endow. Rapid double 8-nm steps by a kinesin mutant.EMBO J. 23, 2993-2999, (2004).
  21. *Yanai, M., J.P. Butler, T. Suzuki. H. Sasaki and H. Higuchi. Regional rheological differences in locomoting neutrophils. Am. J. Physiol. 287, C603-611, (2004).
  22. Kaseda, K., H. Higuchi and *K. Hirose. Alternate fast and slow stepping of a heterodimeric kinesin molecule. Nature Cell Biol. 5, 1079-1082, (2003).
  23. Nguyen, V.T., Y. Kamio and *H. Higuchi. Single-molecule imaging of cooperative assembly of gamma-hemolysin on erythrocyte membranes. EMBO J. 22, 4968-4979, (2003).
  24. Okada, Y., H. Higuchi and *N. Hirokawa. Proccesivity of the single-headed kinesin KIF1A through biased binding to tubulin. Nature 424, 574-477, (2003).
  25. Kaseda, K., H. Higuchi and *K. Hirose. Coordination of kinesin's two heads studied with mutant heterodimer. Proc. Natl. Acad. Sci. 96, 18058-16063, (2002).
  26. Nguyen, V.T., *H. Higuchi and Y. Kamio. Controlling pore assembly of staphylococcal gamma-hemolysin by low temperature and by disulfide bond formation in double-cystein LukF mutants. Mol. Microbiol. 45, 1485-1498, (2002).
  27. Nishiyama, M., *H. Higuchi and T. Yanagida. Chemomechanical coupling of the forward and backward steps of single kinesin molecules. Nature Cell Biol. 4, 790-797, (2002).
  28. *Shinohara, K., G. Kato, H. Minami and H. Higuchi. Single molecule of a pi-Conjugated polymer slowly twinkles in solution at room temperature. Polymer 42, 8483-8487, (2001).
  29. Nishiyama, M., E. Muto, Y. Inoue, *T. Yanagida and H. Higuchi. Substeps within the 8 nm step per ATPase cycles of single kinesin molecules. Nature Cell Biol. 4, 425-428, (2001).
  30. *Shinohara, K., S. Yamaguchi and H. Higuchi. Single Molecule imaging of a pi-conjugated polymer in tetrahydrofuran solution at room temperature. Polymer J. 32, 977-979, (2000).
  31. *Endow, S.A. and H. Higuchi. Amutant of the motor protein kinesin that moves in both directions on microtubules. Nature 406, 913-916, (2000).
  32. Hirakawa, E., H. Higuchi and *Y.Y. Toyoshima. Processive movement of single 22S dynein molecules occurs only at low ATP concentrations. Proc. Natl. Acad. Sci. USA. 97, 2533-2537, (2000).
  33. Iwatani, S., A.H. Iwane, *H. Higuchi, Y. Ishii and T. Yanagida. Mechanical and chemical properties of cysteine modified kinesin molecules. Biochemistry 38, 10318-10323, (1999).
  34. *Shingyouji, C., H. Higuchi, M. Yoshimura, E. Katayama and T. Yanagida. Dynein arms are oscillating force generators. Nature 393, 711-714, (1998).
  35. Ishijima, A., H. Kojima, T. Funatsu, M. Tokunaga, H. Higuchi, H. Tanaka and *T. Yangagida. Simultaneous observation of individual ATPase and mechanical events by a single myosin molecule during interaction with actin. Cell 92, 161-171, (1998).
  36. Kojima, H., E. Muto, *H. Higuchi and T. Yanagida. Mechanics of single kinesin molecules measured by optical trapping nanometry. Biophys. J. 73, 2012-2022, (1997).
  37. Inoue, Y., Y.Y. Toyoshima, A.H. Iwane, S Morimoto, *H. Higuchi and T. Yanagida. Movement of truncated kinesin fragments with a short or an artificial flexible neck. Proc. Natl. Acad. Sci. USA. 94, 7275-7280, (1997).
  38. *Higuchi, H., E. Muto, Y. Inoue and T. Yanagida. Kinetics of force generation of single kinesin molecules activated by photolysis of caged ATP. Proc. Natl. Acad. Sci. USA. 94, 4395-4400, (1997).
  39. West, J.M., H. Higuchi, A. Ishijima and *T. Yanagida. Modification of the bi-directional sliding movement of actin filaments along native thick filaments isolated from a clam. J. Muscle Res. Cell Motil. 17, 637-646, (1996).
  40. Ishijima, A., H. Kojima, H. Higuchi, Y. Harada, T. Funatsu and *T. Yanagida. Multiple- and single-molecule analysis of the actomyosin motor by nanometer-piconewton manipulation with a microneedle: unitary steps and forces. Biophys. J. 70, 383-400, (1996).
  41. Higuchi, H., and *Y.E. Goldman. Sliding distance per ATP molecule hydrolyzed by myosin heads during isotonic shortening of skinned muscle fibers. Biophys. J. 69, 1491-1507, (1995).
  42. Higuchi, H., T. Yanagida and *Y.E. Goldman. Compliance of thin filaments in skinned fibers of rabbit skeletal muscle. Biophys. J. 69, 1000-1010, (1995).
  43. Ishijima, A., Y. Harada, H. Kojima, T. Funatsu, H. Higuchi and *T. Yanagida. Single-molecule analysis of the actomyosin motor using nano-manipulation. Biochem. Biophys. Res. Comm. 199, 1057-1063, (1994).
  44. Manabe T., Y. Kawamura, H. Higuchi, S. Kimura and *K. Maruyama. Connectin, giant elastic protein, in giant sarcomeres of clay claw muscle. J. Muscle Res. Cell Motil. 14, 654-665, (1993).
  45. Higuchi, H., Y. Nakauchi, K. Maruyama and *S. Fujime. Characterization of gamma-connectin (titin) from striated muscle by dynamic light scattering. Biophys. J. 65, 1906-1915, (1993).
  46. *Fujime, S. and H. Higuchi. An analysis of the dynamic light scattering spectra of wormlike chains: beta-connectin from striated muscle. Macromolecules. 26, 6261-6266, (1993).
  47. Funatsu, T., E. Kono, H. Higuchi, S. Kimura, S. Ishiwata, T. Yoshioka, K. Maruyama and *S. Tsukita. Elastic filaments in situ in cardiac muscle: Deep-etch replica analysis in combination with selective removal of actin and myosin filaments. J. Cell Biol. 120, 711-724, (1993).
  48. *Higuchi, H., T. Suzuki, S. Kimura, T. Yoshioka, K. Maruyama and Y. Umazume. Localization and elasticity of connectin (titin) filaments in skinned frog muscle fibers subjected to partial depolymerization of thick filaments. J. Muscle Res. Cell Motil. 13, 285-292, (1992).
  49. *Higuchi, H. Changes in contractile properties with selective digestion of connectin (titin) in skinned fibers of frog skeletal muscle. J. Biochem. 111, 291-295, (1992).
  50. *Umazume, Y., H. Higuchi and S. Takemori. Myosin heads contact with thin filaments in compressed relaxed skinned fibres of frog skeletal muscle. J. Muscle Res. Cell Motil. 12, 466-471, (1991).
  51. Higuchi, H., and *Y.E. Goldman. Sliding distance between actin and myosin filaments per ATP molecule hydrolyzed in skinned muscle fibers. Nature 352, 352-354, (1991).
  52. Konishi, M., *K. Wakabayashi, S. Kurihara, H. Higuchi, N. Onodera, Y. Umazume, H. Tanaka, T. Hamanaka and Y. Amemiya. Time-resolved synchrotron X-ray diffraction studies of a single frog skeletal muscle fiber: Time courses of intensity changes of the equatorial reflections and intracellular Ca2+ transients. Biophys. Chem. 39, 287-297, (1991).
  53. Funatsu, T., H. Higuchi and *S. Ishiwata. Elastic filaments in skeletal muscle revealed by selective removal of thin filaments with plasma gelsolin. J. Cell. Biol. 110, 53-62, (1990).
  54. *Higuchi, H. and S. Takemori. Butanedione monoxime suppresses contraction and ATPase activity of rabbit skeletal muscle. J. Biochem. 105, 638-643, (1989).
  55. *Maruyama, K., A. Matsuno, H. Higuchi, S. Shimaoka, S. Kimura and T. Shimizu. Behaviour of connectin (titin) and nebulin in skinned muscle fibers released after extreme stretch as revealed by immunoelectron microscopy. J. Muscle Res. Cell Motil. 10, 350-359, (1989).
  56. Higuchi, H., T. Yoshioka and *K. Maruyama. Positioning of actin filaments and tension generation in skinned muscle fibers released after stretch beyond overlap of the actin and myosin filaments. J. Muscle Res. Cell Motil. 9, 491-498, (1988).
  57. Kamei, T., S. Kakuta and *H. Higuchi. Biased Binding of Single Molecules and Continuous Movement of Multiple Molecules of Truncated Single-Headed Kinesin. Biophysical J. 88, 2068-2077, (2005).
  58. Itoh, Y., T. Suzuki, S. Kimura, K. Ohashi, H. Higuchi, H. Sawada, T. Shimizu, M. Shibata and *K. Maruyama. Extensible and less extensible domains of connectin filaments in stretched vertebrate skeletal muscle sarcomeres as detected by immunofluorescence and immunoelectron microscopy using monoclonal antibodies. J. Biochem. 104, 504-508, (1988).
  59. *Horiuti, K., H. Higuchi, Y. Umazume, M. Konishi, O. Okazaki and S. Kurihara. Mechanism of action of 2, 3-butanedione 2-monoxime on contraction of frog skeletal muscle fiber. J. Muscle Res. Cell Motil. 156-164, (1988).
  60. Mitsui, Y., H. Higuchi, S. Terashima, S. Takahashi, D.H. Hu, *K. Maruyama and H. Noda. Elastic properties and b-sheet structure of connectin threads. J. Biochem. 102, 1483-1487, (1987).
  61. *Higuchi. H. Lattice swelling in single skinned fibers of frog muscle by the selective digestion of the elastic component. Biophys. J. 52, 29-32, (1987).
  62. Higuchi, H., T. Funatsu, A. Ishijima, N. Okanura and *S. Ishiwata. Accumulated strain mechanism for length determination of thick filaments in skeletal muscle. I. Experimental basis. J. Muscle Res. Cell Motil. 7, 491-500, (1986).
  63. Higuchi, H. and *Y. Umazume. Lattice shrinkage with increasing resting tension in stretched single skinned fibers of frog muscle. Biophys. J. 50, 385-389, (1986).
  64. *Umazume, Y., S. Onodera and H. Higuchi. Width and lattice spacing in radially compressed frog skinned muscle fibers at various pH value, magnesium ion concentrations and ionic strengths. J. Muscle Res. Cell Motil. 7, 251-258, (1986).
  65. Yoshioka, T., H. Higuchi, S. Kimura, K. Ohashi, Y. Umazume and *K. Maruyama. Effects of mild trypsin treatment on the passive tension generation and connectin splitting in stretched skinned fibers from frog skeletal muscle. Biomed. Res. 7, 181-186, (1986).
  66. *Maruyama, K., T. Yoshioka, H. Higuchi, K. Ohashi, S. Kimura and R. Natori. Connectin filaments link thick filaments and Z lines in frog skeletal muscle as revealed by imunoelectron microscopy. J. Cell Biol. 101, 2167-2172, (1985).
  67. Higuchi, H. and *Y. Umazume. Localization of the parallel elastic components in frog skinned muscle fibers studied by the dissociation of the A- and I-bands. Biophys. J. 48, 137-147, (1985).
  68. Higuchi, H. and *S. Ishiwata. Disassembly kinetics of thick filaments in a rabbit skeletal muscle fiber. Effects of ionic strength, Ca ion concentration, pH, temperature and cross-bridges on the stability of thick filament structure. Biophys. J. 47, 267-275, (1985).
  69. *Ishiwata, S., K. Muramatsu and H. Higuchi. Disassembly from both ends of thick filaments in a rabbit skeletal muscle fiber. An optical diffraction study. Biophys. J. 47, 257-266, (1985).
  70. *Maruyama, K., H. Sawada, S. Kimura, K. Ohashi, H. Higuchi and Y. Umazume. Connectin filaments in stretched skinned fibers of frog skeletal muscle. J. Cell Biol. 99, 1391-1397, (1984).

Motoshi Kaya

  1. Kaya M. and H. Higuchi*.(2010)Nonlinear Elasticity and an 8-nm Working Stroke of Single Myosin Molecules in Myofilaments. Science, 329, 686-689
  2. Jinha A., Ait-Haddou R., Kaya M. and Herzog W. (2009) A task-specific validation of homogeneous non-linear optimisation approaches. Journal of Theoretical Biology 259, 695-700.
  3. Kaya, M., Leonard, T.R. and Herzog, W. (2008) Premature deactivation of soleus during the propulsive phase of cat jumping. Journal of Royal Society Interface 5, 415-426.
  4. Kaya, M., Leonard, T.R. and Herzog, W. (2006) Control of ground reaction forces by hindlimb muscles during cat locomotion. Journal of Biomechanics 39, 2752-2766.
  5. Kaya, M., Jinha A, Leonard, T.R. and Herzog, W. (2005) Multi-functionality of the cat medical gastrocnemius during locomotion. Journal of Biomechanics 38, 1291-1301.
  6. Hase, K, Kaya, M., Zavatsky, A.B. and Halliday, S.E. (2004) Muscle loads in Ergometer rowing. Journal of Applied Biomechanics 20, 317-323.
  7. Kaya, M., Leonard, T. and Herzog, W. (2003) Coordination of cat medial gastrocnemius and soleus during cat locomotion. Journal of Experimental Biology 206, 3645-3655.
  8. Hase, K., Kaya, M., Yamazaki, N., Andrews, B.J., Zavatsky, A.B. and Halliday, S.E. (2002) Biomechanics of rowing I. A model analysis of musculoskeletal loads in rowing for fitness. JSME International Journal Series C45, 1073-1081.
  9. Kaya, M., Carvalho, W., Leonard, T. and Herzog, W. (2002) Estimation of cat medial gastrocnemius fascicle lengths during dynamic contractions. Journal of Biomechanics 35, 893-902.
  10. Wakeling, J.M., Kaya, M., Temple, G.K., Johnston, I.A. and Herzog, W. (2002) Motor unit recruitment during locomotion. Journal of Experimental Biology 205, 359-369.

Sayaka Kita

:: Under Construction ::

Seine Shintani

:: Under Construction ::

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