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Related Experiment Videos

Nuclear targeting by the growth factor midkine.

Yoshihisa Shibata1, Takashi Muramatsu, Makoto Hirai

  • 1Department of Biochemistry, Nagoya University School of Medicine, Showa-ku, Japan.

Molecular and Cellular Biology
|September 7, 2002
PubMed
Summary

Low-density lipoprotein receptor-related protein (LRP) mediates nuclear targeting of midkine, a heparin-binding growth factor. This nuclear translocation, facilitated by nucleolin, is crucial for midkine

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Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Ligand-receptor internalization is typically linked to cellular desensitization.
  • Low-density lipoprotein receptor-related protein (LRP) is a key endocytosis receptor.
  • LRP binds various ligands, including heparin-binding growth factor midkine.

Purpose of the Study:

  • To investigate the role of LRP in midkine internalization and nuclear targeting.
  • To determine the biological significance of midkine nuclear translocation.
  • To elucidate the involvement of nucleolin in midkine's intracellular journey.

Main Methods:

  • Utilizing LRP-deficient cells and LRP-expressing transfectants.
  • Tracking exogenous midkine's localization using microscopy.

Related Experiment Videos

  • Mapping midkine-binding sites on nucleolin.
  • Employing mutant nucleolin lacking a nuclear localization signal.

    • Main Results:

    • LRP mediates midkine internalization and nuclear targeting.
    • Intact midkine reaches the nucleus within 20 minutes.
    • Midkine binds to nucleolin in the cytoplasm; binding sites identified in nucleolin's N-terminal domain.
    • Mutant nucleolin impairs midkine nuclear translocation and suppresses its cell survival-promoting activity.

    Conclusions:

    • LRP plays a novel role in intracellular signaling via its ligand, midkine.
    • Nuclear targeting of midkine, dependent on LRP and nucleolin, is essential for its biological functions, particularly cell survival.
    • This study highlights a new pathway for LRP-mediated signaling and the critical role of nucleolin.