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Author Spotlight: Optogenetic Inhibition of Rho1-Mediated Actomyosin Contractility Coupled with Measurement of Epithelial Tension in Drosophila Embryos
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Author Spotlight: Optogenetic Inhibition of Rho1-Mediated Actomyosin Contractility Coupled with Measurement of Epithelial Tension in Drosophila Embryos

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Spatiotemporal control of actomyosin contractility by MRCKβ signaling drives phagocytosis

Ceniz Zihni1, Anastasios Georgiadis1,2, Conor M Ramsden1

  • 1UCL Institute of Ophthalmology, University College London, London, UK.

The Journal of Cell Biology
|September 19, 2022
PubMed

Insights

Actomyosin contractility, regulated by MRCKβ signaling, is crucial for retinal pigment epithelium (RPE) phagocytosis. This pathway ensures proper particle internalization and maintains retinal integrity, offering potential therapeutic targets for vision disorders.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Ophthalmology

Background:

  • Phagocytosis is a critical cellular process involving actin dynamics.
  • The role of actomyosin contractility in phagocytosis, particularly in the retinal pigment epithelium (RPE), remains incompletely understood.

Purpose of the Study:

  • To elucidate the role of actomyosin contractility in RPE phagocytosis.
  • To identify the molecular mechanisms linking phagocytic receptor activation to cytoskeletal rearrangements.

Main Methods:

  • Utilized RPE cell cultures and in vivo models.
  • Investigated the phosphorylation and activation of signaling molecules including Dbl3, MRCKβ, and myosin-II.
  • Assessed the impact of genetic and pharmacologic manipulations on phagocytic cup formation and particle internalization.

Main Results:

  • Particle binding to Mer Tyrosine Kinase (MerTK) activates MRCKβ/myosin-II and N-WASP, driving membrane deformation and cup formation.
  • Sustained MRCKβ/myosin-II activity facilitates cytoskeletal force transmission for cup closure and particle internalization.
  • MRCKβ is essential for RPE phagocytosis in vivo and rescues phagocytosis in MerTK-deficient cells.
  • MRCKβ also plays a role in Fc receptor-mediated phagocytosis.

Conclusions:

  • MRCKβ signaling at the cell cortex spatiotemporally regulates actomyosin contractility during phagocytosis in the RPE.
  • This pathway is a principal effector downstream of MerTK and is crucial for maintaining retinal integrity.
  • Targeting MRCKβ signaling may offer therapeutic benefits for vision disorders characterized by phagocytic dysfunction.

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