Sorcin couples Annexin A11 recruitment to ESCRT-III assembly for plasma membrane repair

Jordan Matthew Ngo1, Justin Krish Williams1, Abinayaa Murugupandiyan1

  • 1Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720.

Insights

Animal cells lack cell walls, making plasma membrane (PM) repair crucial. Sorcin acts as a key factor, linking PM damage sensing to ESCRT-III assembly for effective membrane repair.

Area of Science:

  • Cell Biology
  • Membrane Biology
  • Biochemistry

Background:

  • Animal cells' lack of a cell wall makes them vulnerable to plasma membrane (PM) damage.
  • Maintaining PM integrity is vital for cell survival, and defects in PM repair are linked to diseases like muscular dystrophy.
  • Annexin and ESCRT proteins are known to be involved in PM repair, but their coordinated recruitment to damage sites is not fully understood.

Purpose of the Study:

  • To elucidate the coordinated recruitment of proteins involved in plasma membrane repair.
  • To identify novel factors that mediate the link between PM damage sensing and the ESCRT-III machinery.

Main Methods:

  • Quantitative organellar proteomics to identify proteins at sites of membrane damage.
  • Genome-wide CRISPR interference screens to identify essential PM repair factors.
  • Biochemical assays to determine protein-protein interactions and Ca2+ dependence.

Main Results:

  • Sorcin was identified as a novel PM repair factor.
  • Sorcin directly binds to annexin A11 (ANXA11) and ALIX in a Ca2+-dependent manner.
  • Sorcin is essential for the recruitment of ESCRT-III to PM lesions, facilitating membrane resealing.

Conclusions:

  • A Ca2+-dependent scaffolding mechanism couples PM damage sensing by ANXA11 to ESCRT-III assembly via sorcin.
  • This mechanism is critical for efficient plasma membrane repair in animal cells.
  • Findings provide new insights into cellular defense against membrane damage and potential therapeutic targets for related diseases.

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