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Filamin is essential for shedding of the transmembrane serine protease, epithin

Chungho Kim1, Yongcheol Cho, Chan-Hee Kang

  • 1School of Biological Sciences, Seoul National University, Kwanak-gu, Shilim-dong, Seoul 151-742, Republic of Korea.

EMBO Reports
|September 20, 2005
PubMed

Insights

Phorbol myristate acetate (PMA) triggers epithin shedding by linking it to the actin cytoskeleton via filamin. This interaction is crucial for epithin release, highlighting filamin

Area of Science:

  • Cell Biology
  • Protease Function
  • Cytoskeletal Dynamics

Background:

  • Epithin, a type II transmembrane serine protease, exists in soluble and membrane-bound forms.
  • Shedding regulates epithin activity, but the triggering intracellular events remain unclear.

Purpose of the Study:

  • To elucidate the intracellular mechanisms regulating epithin shedding.
  • To identify proteins involved in linking epithin to the actin cytoskeleton.

Main Methods:

  • Treatment of cells with phorbol myristate acetate (PMA).
  • Investigation of epithin localization and release.
  • Analysis of actin cytoskeleton involvement and filamin interaction.
  • Use of filamin-deficient cells and metalloprotease inhibitors.

Main Results:

  • PMA induces epithin release and accumulation at cell-cell contacts, dependent on cortical actin.
  • Filamin identified as the linker between epithin and the actin cytoskeleton.
  • PMA enhances epithin-filamin interaction; epithin shedding is impaired in filamin-deficient cells.
  • Epithin release is independent of its protease activity but blocked by metalloprotease inhibitors.

Conclusions:

  • Filamin plays a critical role in epithin shedding by connecting it to the actin cytoskeleton.
  • This linkage facilitates the action of metalloprotease(s) responsible for epithin release.

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