Fc{epsilon}RI-mediated mast cell degranulation requires calcium-independent microtubule-dependent translocation of granules to the plasma membrane

J Cell Biol. 2005 Jul 4;170(1):115-26. doi: 10.1083/jcb.200501111.


The aggregation of high affinity IgE receptors (Fcepsilon receptor I [FcepsilonRI]) on mast cells is potent stimulus for the release of inflammatory and allergic mediators from cytoplasmic granules. However, the molecular mechanism of degranulation has not yet been established. It is still unclear how FcepsilonRI-mediated signal transduction ultimately regulates the reorganization of the cytoskeleton and how these events lead to degranulation. Here, we show that FcepsilonRI stimulation triggers the formation of microtubules in a manner independent of calcium. Drugs affecting microtubule dynamics effectively suppressed the FcepsilonRI-mediated translocation of granules to the plasma membrane and degranulation. Furthermore, the translocation of granules to the plasma membrane occurred in a calcium-independent manner, but the release of mediators and granule-plasma membrane fusion were completely dependent on calcium. Thus, the degranulation process can be dissected into two events: the calcium-independent microtubule-dependent translocation of granules to the plasma membrane and calcium-dependent membrane fusion and exocytosis. Finally, we show that the Fyn/Gab2/RhoA (but not Lyn/SLP-76) signaling pathway plays a critical role in the calcium-independent microtubule-dependent pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Calcium / metabolism
  • Calcium Signaling / drug effects
  • Calcium Signaling / immunology
  • Cell Degranulation / physiology
  • Cell Membrane / immunology*
  • Cells, Cultured
  • Exocytosis / drug effects
  • Exocytosis / immunology
  • Inflammation Mediators / immunology
  • Inflammation Mediators / metabolism
  • Mast Cells / cytology
  • Mast Cells / immunology*
  • Mast Cells / metabolism*
  • Membrane Fusion / drug effects
  • Membrane Fusion / immunology
  • Mice
  • Mice, Inbred C57BL
  • Microtubules / metabolism*
  • Phosphoproteins / metabolism
  • Protein Transport / drug effects
  • Protein Transport / immunology
  • Proto-Oncogene Proteins / metabolism
  • Proto-Oncogene Proteins c-fyn
  • Receptor Aggregation / immunology
  • Receptors, IgE / immunology*
  • Secretory Vesicles / immunology*
  • Secretory Vesicles / metabolism
  • Signal Transduction / drug effects
  • Signal Transduction / immunology
  • rhoA GTP-Binding Protein / metabolism
  • src-Family Kinases / metabolism


  • Adaptor Proteins, Signal Transducing
  • Gab2 protein, mouse
  • Inflammation Mediators
  • Phosphoproteins
  • Proto-Oncogene Proteins
  • Receptors, IgE
  • Fyn protein, mouse
  • Proto-Oncogene Proteins c-fyn
  • src-Family Kinases
  • rhoA GTP-Binding Protein
  • Calcium