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FHL2 interacts with both ADAM-17 and the cytoskeleton and regulates ADAM-17 localization and activity

Matthias Canault1, Edwige Tellier, Bernadette Bonardo

  • 1Inserm, U626, Marseilles, France; Université de la Méditerranée, Faculté de Médecine, Marseilles, Cedex 5, France.

Journal of Cellular Physiology
|April 19, 2006
PubMed

Insights

ADAM-17 interacts with FHL2, influencing its localization and function. This interaction suggests FHL2 plays a key role in regulating ADAM-17 activity and substrate shedding.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • ADAM-17 (a disintegrin and metalloproteinase 17) is crucial for ectodomain shedding of transmembrane proteins.
  • Four and Half LIM domain 2 (FHL2) is a protein involved in various protein-protein interactions.

Purpose of the Study:

  • To investigate the interaction between ADAM-17 and FHL2.
  • To elucidate the functional consequences of this interaction on ADAM-17 activity and localization.

Main Methods:

  • Yeast two-hybrid system to identify protein interactions.
  • Co-localization studies in H9C2 cardiomyoblast cells.
  • Analysis of ADAM-17 substrate shedding in wild-type and FHL2-deficient macrophages.

Main Results:

  • ADAM-17 directly interacts with FHL2, specifically involving amino acids 721-739 of ADAM-17.
  • Both proteins co-localize with the actin cytoskeleton, with FHL2 binding to both ADAM-17 and the cytoskeleton.
  • FHL2 deficiency leads to reduced surface expression of ADAM-17, while wild-type cells show enhanced substrate release upon stimulation.

Conclusions:

  • A physical and functional interaction exists between ADAM-17 and FHL2.
  • FHL2 influences ADAM-17's association with the cytoskeleton and its cell surface presence.
  • FHL2 plays a regulatory role in ADAM-17-mediated ectodomain shedding.

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