Laboratory/Faculty

Laboratory of Cell Regulation
Group of Signaling Mechanisms

ProfessorNaoki Hisamoto
Signal transduction networks in whole organisms, using nematode as a model animal
Associate ProfessorHiroshi Hanafusa
Signal transduction networks mediated by LRRK1 in mammalian cells
Assistant ProfessorStrahil Ivanov Pastuhov
Molecular mechanisms regulating axon regeneration
Senior Research FellowKunihiro Matsumoto
Signal transduction networks regulating development and differentiation
Laboratory HP
Japanese
Naoki Hisamoto Professor
Lab members

Studies of signal transduction networks have provided important insights regarding the regulation of various cellular events, including cell proliferation, differentiation, development, and regeneration.  Signal transduction pathways detect extracellular signals at the cell surface and transmit them through the cytoplasm to nuclear and other intracellular targets.  The mechanisms of intracellular signal transmission involve players that are conserved in organisms as diverse as nematodes and humans.  In our laboratory, we are investigating the molecular mechanisms of signal transduction networks that control various biological regulatory systems in Caenorhabditis elegans and mammalian cultured cells.

Signal transduction cascades in C. elegans as a model animal

The nematode C. elegans is an animal of 1-2 mm length that feeds on bacteria in soil.  Recently, C. elegans has been highlighted as a model multicellular organism because it has many genes that have homologues in mammals.  In addition, C. elegans is useful for genetic and molecular biological analyses.  In our laboratory, we especially focus on clarifying the mechanisms of axon regeneration of injured neurons by functional analysis of the signal transduction networks conserved between nematodes and humans.  Further analysis will elucidate the precise mechanisms by which signal transduction pathways control various cellular events.

Signaling networks mediated by LRRK1 in mammalian cells

LRRK1 is a member of the ROCO family and contains a Ras-like GTPase domain and a MAPKKK-like kinase domain. Recently, another ROCO family member, LRRK2, has been reported to be involved in the pathogenesis of familial Parkinson’s diseases. However, the modes of action of LRRK1 and LRRK2 remain unknown. We found that LRRK1 regulates intracellular trafficking of EGF receptor in a manner dependent on its kinase activity. Furthermore, we revealed that LRRK1 plays an important role in centrosome maturation in M-phase. We are now focusing on two projects: (1) determining the mechanism regulating LRRK1 kinase activity; and (2) identification of target proteins phosphorylated by LRRK1 in EGFR trafficking and M-phase.

Fig 1. Photo of a regenerating axon

Fig 2. Functions of LRRK1

References

  1. Alam, T. et al. Nature Commun. 7, 10388, 2016.
  2. Hanafusa, H. et al. Nature Cell Biol. 17, 106, 2015.
  3. Hisamoto N. et al. Cell Rep. 9, 1628, 2014.
  4. Li C. et al. Nature Neurosci. 15, 551, 2012.
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  6. Hanafusa H. et al. Nature Communn. 2, 158, 2011.
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