Takeshi Nakamura

Division of Biosignaling

Research theme

  • Neurite outgrowth and axon guidance My research seeks to answer 2 questions: What are the common requirements for regulating neuritogenesis? What signaling molecules coordinate the regulation of cytoskeletal organization and membrane addition/removal during neuritogenesis? To address these issues, we are investigating the following topics:
    i) The mechanism underlying the neurite-promoting effect of TC10 through vesicle exocytosis, and the physiological role of TC10 in neuronal development and regeneration.
    ii) The role of Rab35 in neuronal function, and the regulation of Rab35 activity in neuronal cells.
  • Molecular mechanisms that regulate the transition from early endosome to late endosome and lysosome (neuronal and non-neuronal cells).
  • Molecular mechanisms that regulate neurotransmission.
  • Development of new modalities in FRET imaging.
  • Mathematical modeling of the molecular mechanisms that regulate growth cone advance.

Selected publications from the past 5 years:

  • Morishita S, Wada N, Fukuda M, and Nakamura T: Rab5 activation on macropinosomes requires ALS2, and its subsequent inactivation through ALS2 detachment requires active Rab7. FEBS Lett. 593, 230-241 (2019)
  • Koinuma S, Takeuchi K, Wada N, and Nakamura T: cAMP-induced activation of protein kinase A and p190B RhoGAP mediates down-regulation of plasmalemmal TC10 GTPase activity and neurite outgrowth. Genes Cells. 22, 953-967 (2017)
  • Yasuda S, Morishita S, Fujita A, Nanao T, Wada N, Waguri S, Schiavo G, Fukuda M, and Nakamura T: Mon1-Ccz1 activates Rab7 only on late endosome and dissociates from lysosome in mammalian cells. J. Cell Sci. 129, 329-340 (2016)
  • Fujita, A., Koinuma, S., Yasuda, S., Nagai, H., Kamiguchi, H., Wada, N., and Nakamura, T. GTP hydrolysis of TC10 promotes neurite outgrowth through exocytic fusion of Rab11- and L1-containing vesicles by releasing exocyst component Exo70. PLoS One, PLoS One 8, e79689 (2013).
  • Nakamura, T., Yasuda, S., Nagai, H., Koinuma, S., Morishita, S., Goto, A., Kinashi, T., and Wada, N. Longest neurite-specific activation of Rap1B in hippocampal neurons contributes to polarity formation through RalA and Nore1A in addition to PI3-kinase. Genes Cells 18, 1020-1031 (2013)
  • Nagai, H., Yasuda, S., Ohba, Y., Fukuda, M, and Nakamura, T. All members of the EPI64 subfamily of TBC/RabGAPs also have GAP activities toward Ras. J. Biochem. 153, 283-288 (2013).
  • Goto A, Hoshino M, Matsuda M, Nakamura, T: Phosphorylation of STEF by protein kinase A is critical for Rac1 activation and neurite outgrowth in dbcAMP-treated PC12D cells. Mol. Biol. Cell 22, 1780-1790 (2011).
  • Kiyokawa E, Aoki K, Nakamura T, Matsuda M: Spatiotemporal regulation of small GTPases as revealed by genetically encoded probes based on Forster resonance energy transfer (FRET): implications for signaling and pharmacology. Ann. Rev. Pharm. 51, 337-358. (2010).
  • Nakamura T, Matsuda M: in vivo imaging of signal transduction cascades with probes based on Forster Resonance Energy Transfer. in Current Protocols in Cell Biology. John Wiley & Sons, Hoboken Chapter 14, Unit 14.10. (2009).
  • Nakamura T, Aoki K, Matsuda M: FRET imaging and in silico simulation: analysis of the signaling network of nerve growth factor-induced neuritogenesis. Brain Cell Biol. 36, 19-30. (2008).
  • Kitano M, Nakaya M, Nakamura T, Nagata S, Matsuda M: Imaging of Rab5 activity identifies essential regulators for phagosome maturation. Nature 453, 241-245 (2008).
  • Aoki K, Nakamura T, Inoue T, Meyer T, Matsuda M: An essential role for the SHIP2-dependent negative feedback loop in neuritogenesis of nerve growth factor-stimulated PC12 cells. J. Cell Biol. 177, 817-827 (2007).
  • Kawase K, Nakamura T, Takaya A, Aoki K, Namikawa K, Kiyama K, Inagaki S, Takemoto H, Saltiel AS, Matsuda M : GTP hydrolysis by the Rho-family GTPase TC10 promotes exocytic vesicle fusion. Dev. Cell 11, 411-421 (2006).
  • Nakamura T, Kurokawa K, Kiyokawa E, Matsuda M: Analysis of the spatio-temporal regulation of Rho GTPases using Raichu probes. Methods Enzymol. 406, 315-332 (2006).