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Tollip antagonizes ESCRT-III-mediated plasma membrane repair and cell recovery

Julia M Ferrick1,2, Xinan Meng3, Emily Morgan1,2

  • 1Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, 15213, USA.

Cell Regeneration (London, England)
|May 19, 2026
PubMed

Insights

Toll-interacting protein (Tollip) regulates cell recovery from plasma membrane damage. Tollip deficiency enhances membrane repair and cell survival by modulating ESCRT-III, linking membrane integrity to immune signaling.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Immunology

Background:

  • Cells repair plasma membrane (PM) ruptures via ESCRT-III machinery.
  • Regulation of PM repair remains largely unknown.

Purpose of the Study:

  • Identify regulators of ESCRT-III-mediated PM repair.
  • Investigate the role of Toll-interacting protein (Tollip) in PM repair and cell recovery.

Main Methods:

  • Quantitative proteomics to identify proteins at damaged PM.
  • Microscopy assays in mammalian cells and C. elegans to visualize Tollip recruitment.
  • Cell survival assays after PM damage.
  • Calcium influx measurements.

Main Results:

  • Tollip was identified as a conserved negative regulator of ESCRT-III-mediated PM repair.
  • Tollip localized to PM injury sites, independent of Ca2+ influx.
  • Tollip deficiency enhanced ESCRT-III assembly, PM repair, and long-term cell survival.
  • Tollip overexpression suppressed PM repair and cell survival.
  • Tollip modulated chemokine and cytokine production via the plasma-membrane-integrity (PMI) pathway.

Conclusions:

  • Tollip acts as a molecular rheostat controlling the balance between PM repair and immune signaling.
  • Tollip links membrane damage response to cell recovery and innate immunity.
Keywords:
Cell recoveryESCRT-IIINecroptosisPlasma membrane damagePlasma membrane integrity pathwayPlasma membrane repairProgrammed cell deathTollip

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