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A FRET biosensor for necroptosis uncovers two different modes of the release of DAMPs

Shin Murai1, Yoshifumi Yamaguchi2, Yoshitaka Shirasaki3,4

  • 1Department of Biochemistry, Toho University School of Medicine, 5-21-16 Omori-Nishi, Ota-ku, Tokyo, 143-8540, Japan.

Nature Communications
|October 28, 2018
PubMed

Insights

Researchers developed a novel FRET biosensor, SMART, to monitor necroptosis by tracking MLKL activation. This tool, combined with LCI-S, revealed new mechanisms for DAMP release from necroptotic cells.

Area of Science:

  • Cellular biology
  • Molecular mechanisms of cell death

Background:

  • Necroptosis is a regulated form of necrosis crucial in pathology.
  • The release of danger-associated molecular patterns (DAMPs) from dying cells is incompletely understood.

Purpose of the Study:

  • To develop a biosensor for monitoring necroptosis.
  • To investigate the mechanisms of DAMP release during necroptosis.

Main Methods:

  • Development of a FRET biosensor (SMART) for MLKL activation.
  • Utilizing SMART in conjunction with Live-Cell Imaging for Secretion activity (LCI-S).

Main Results:

  • SMART specifically monitors necroptosis, not apoptosis or other necrosis forms.
  • SMART tracks plasma membrane translocation of activated MLKL.
  • Two distinct modes of High Mobility Group Box 1 release were identified.

Conclusions:

  • SMART is a novel tool for studying necroptosis.
  • Novel regulatory mechanisms for DAMP release during necroptosis were uncovered.

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