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MERTK coordinates efferocytosis by regulating integrin localization and activation

Brandon H Dickson1, Tarannum Tasnim1, Rachel A Nicholson1

  • 1Department of Microbiology and Immunology, and the Western Infection, Immunity and Inflammation Centre, The University of Western Ontario, London, Ontario, N6A 5C1, Canada.

Journal of Cell Science
|February 20, 2026
PubMed

Insights

Efferocytosis, the engulfment of apoptotic cells, is mediated by MERTK receptor complexes. These complexes involve β2 integrins and signaling molecules, revealing new mechanisms for cellular clearance and inflammatory disease insights.

Area of Science:

  • Cell Biology
  • Immunology
  • Molecular Biology

Background:

  • Efferocytosis is crucial for tissue homeostasis and preventing autoimmunity.
  • The MERTK receptor tyrosine kinase mediates efferocytosis in many tissues.
  • The precise signaling pathways and molecular mechanisms of MERTK-mediated efferocytosis remain largely unknown.

Purpose of the Study:

  • To elucidate the molecular mechanisms and signaling pathways governing MERTK-mediated efferocytosis.
  • To identify the protein components of MERTK-containing receptor complexes involved in efferocytosis.

Main Methods:

  • Mass spectrometry was employed to identify proteins within MERTK receptor complexes.
  • Super-resolution microscopy was utilized to visualize the structure and dynamics of these complexes during efferocytosis.
  • Functional assays assessed the roles of MERTK and β2 integrins in apoptotic cell engulfment.

Main Results:

  • Identified 180 nm receptor complexes containing MERTK, β2 integrins, and associated signaling molecules.
  • Demonstrated that MERTK induces a PI3-kinase-dependent conformational change in β2 integrins, promoting high-affinity binding.
  • Characterized a highly structured efferocytic synapse with MERTK at the center and an expanding ring of β2 integrins and actin at the leading edge, dependent on Src family kinases and FAK.

Conclusions:

  • MERTK and β2 integrins cooperate to mediate efferocytosis through a structured signaling pathway.
  • The findings provide novel insights into the function of MERTK in cellular clearance.
  • Understanding these mechanisms may illuminate the contribution of MERTK defects to inflammatory and autoimmune diseases.
Keywords:
EfferocytosisIntegrinMERTKMacrophagesSignaling

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