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Receptor dynamics regulates actin polymerization state through phosphorylation of cofilin in mast cells

Ruriko Suzuki1, Yoshikazu Inoh2, Satoru Yokawa2

  • 1Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya, 467-8603, Japan.

Biochemical and Biophysical Research Communications
|November 21, 2020
PubMed

Insights

Multivalent antigens trigger mast cell actin depolymerization via cofilin dephosphorylation. Monomer haptens reverse this by promoting cofilin phosphorylation, restoring actin polymerization and cell function.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Mast cell activation is initiated by IgE receptor (FcεRI) aggregation.
  • Actin polymerization dynamics are crucial for FcεRI-mediated mast cell activation.
  • The precise relationship between FcεRI aggregation/disaggregation and mast cell actin rearrangement remains unclear.

Purpose of the Study:

  • To investigate the role of FcεRI aggregation and disaggregation in mast cell actin dynamics.
  • To elucidate the involvement of cofilin phosphorylation in FcεRI-mediated actin remodeling.
  • To determine the contribution of intracellular calcium changes to these processes.

Main Methods:

  • Stimulation of mast cells with multivalent antigens and monomer haptens.
  • Assessment of actin polymerization state.
  • Measurement of cofilin phosphorylation levels.
  • Manipulation of extracellular calcium and use of actin inhibitors (jasplakinolide).

Main Results:

  • Multivalent antigen stimulation caused rapid actin depolymerization and cofilin dephosphorylation.
  • Subsequent addition of monomer hapten rapidly restored actin polymerization and increased cofilin phosphorylation.
  • Changes in extracellular calcium alone did not restore cofilin phosphorylation, indicating calcium decrease is not the primary driver.
  • Monomer hapten-induced actin re-polymerization was efficient in cells with intact F-actin.

Conclusions:

  • Multivalent antigen-induced actin depolymerization is mediated by cofilin dephosphorylation.
  • Monomer hapten-induced actin re-polymerization occurs via cofilin phosphorylation, independent of significant extracellular calcium reduction.
  • This study clarifies the dynamic interplay between FcεRI signaling and the actin cytoskeleton in mast cells.

Keywords:
CofilinF-actinHaptenMast cellReceptor dynamics

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