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Small GTPase proteins Rin and Rit Bind to PAR6 GTP-dependently and regulate cell transformation

Mitsunobu Hoshino1, Tamotsu Yoshimori, Shun Nakamura

  • 1Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan. hoshinom@ncnp.go.jp

The Journal of Biological Chemistry
|April 16, 2005
PubMed

Insights

Novel small GTPases Rin and Rit bind to PAR6, forming a complex with Rac/Cdc42. This ternary complex promotes cell transformation, suggesting a role in tumorigenesis.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Small GTPases Rin and Rit, related to Ras, are implicated in neuronal differentiation.
  • The direct effectors of Rin and Rit remain largely uncharacterized.
  • PAR6 is a key regulator of cell polarity.

Purpose of the Study:

  • To identify direct effectors of Rin and Rit.
  • To investigate the interaction between Rin/Rit and PAR6.
  • To elucidate the functional consequences of the Rin/Rit-PAR6 interaction.

Main Methods:

  • In vivo and in vitro binding assays to assess GTP-dependent interactions.
  • Co-immunoprecipitation to detect ternary complex formation.
  • NIH3T3 cell transformation assays to evaluate functional effects.

Main Results:

  • Rin and Rit directly bind to the PDZ domain of PAR6 in a GTP-dependent manner.
  • Rin and Rit form a ternary complex with PAR6 and Rho GTPases Rac/Cdc42.
  • This ternary complex synergistically enhances NIH3T3 cell transformation.
  • The Rin/Rit-PAR6 interaction is crucial for potentiating cell transformation.

Conclusions:

  • The Rin/Rit-PAR6-Rac/Cdc42 ternary complex is a novel functional unit.
  • This complex plays a significant role in potentiating cell transformation.
  • The findings suggest a potential physiological role for this complex in tumorigenesis.

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