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ALOX15 links lipid metabolism to receptor trafficking in platelet activation

Yosef Eshetie Amare1,2, Sharad Saxena1, Serena Zacchigna1,3

  • 1Cardiovascular Biology Laboratory, International Centre for Genetic Engineering and Biotechnology (ICGEB), Trieste, Italy.

The FEBS Journal
|June 29, 2026
PubMed

Insights

Researchers discovered a new way platelet activation is controlled. Lipid mediators influence receptor myristoylation, aiding membrane localization and platelet function, offering new therapeutic targets for bleeding disorders.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Hematology

Background:

  • Platelet activation is a complex signaling process.
  • Receptor engagement is the traditional trigger for platelet activation.
  • The role of lipid metabolism in platelet receptor regulation is not fully understood.

Purpose of the Study:

  • To investigate the role of lipid metabolism in platelet activation.
  • To identify novel regulatory mechanisms in platelet signaling.
  • To explore the link between lipid mediators, receptor trafficking, and platelet function.

Main Methods:

  • Analysis of lipid mediators derived from ALOX15.
  • Investigation of Protein Kinase C theta (PKCθ) and N-myristoyltransferase 1 (NMT1) involvement.
  • Assessment of Protease-Activated Receptor 4 (PAR4) myristoylation and membrane localization.

Main Results:

  • ALOX15-derived lipid mediators promote PKCθ-NMT1-dependent myristoylation of PAR4.
  • Myristoylation facilitates PAR4 membrane localization, enhancing platelet activation.
  • This identifies a novel regulatory pathway linking lipid metabolism to receptor trafficking.

Conclusions:

  • Receptor lipidation and trafficking are active regulatory mechanisms in platelet activation.
  • The findings reveal a new layer of control in hemostasis.
  • This suggests potential therapeutic strategies targeting lipid metabolism for hemostatic modulation.
Keywords:
ALOX15PAR4Plateletslipid metabolismreceptor trafficking

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