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

Nishida K, Yamasaki S, Ito Y, Kabu K, Hattori K, Tezuka T, Nishizumi H, Kitamura D, Goitsuka R, Geha RS, Yamamoto T, Yagi T, Hirano T - J. Cell Biol. (2005)

Bottom Line: Drugs affecting microtubule dynamics effectively suppressed the FcepsilonRI-mediated translocation of granules to the plasma membrane and degranulation.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Kanagawa 230-0045, Japan.

ABSTRACT
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.

Show MeSH
Calcium-independent microtubule-dependent pathway is required for FcɛRI-mediated degranulation in mast cells. The FcɛRI-mediated signaling pathway can be dissected into calcium-dependent and calcium-independent pathways. The calcium-independent pathway is critical for microtubule-dependent translocation of granules to the plasma membrane, and this pathway is regulated by Fyn/Gab2/RhoA signaling.
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fig7: Calcium-independent microtubule-dependent pathway is required for FcɛRI-mediated degranulation in mast cells. The FcɛRI-mediated signaling pathway can be dissected into calcium-dependent and calcium-independent pathways. The calcium-independent pathway is critical for microtubule-dependent translocation of granules to the plasma membrane, and this pathway is regulated by Fyn/Gab2/RhoA signaling.

Mentions: The presence of a calcium-independent pathway was suggested previously by a study showing that Fyn-deficient BMMCs have an impaired FcɛRI-induced mast cell degranulation, but an intact calcium influx (Parravicini et al., 2002). Taking this and our findings together, we propose that the mast cell degranulation process can be dissected into two steps: the calcium-independent and microtubule-dependent process and the calcium-dependent one. The former step is involved in the translocation of granules to the plasma membrane, the latter involved in the fusion of granule with the plasma membrane and exocytosis (Fig. 7).


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

Nishida K, Yamasaki S, Ito Y, Kabu K, Hattori K, Tezuka T, Nishizumi H, Kitamura D, Goitsuka R, Geha RS, Yamamoto T, Yagi T, Hirano T - J. Cell Biol. (2005)

Calcium-independent microtubule-dependent pathway is required for FcɛRI-mediated degranulation in mast cells. The FcɛRI-mediated signaling pathway can be dissected into calcium-dependent and calcium-independent pathways. The calcium-independent pathway is critical for microtubule-dependent translocation of granules to the plasma membrane, and this pathway is regulated by Fyn/Gab2/RhoA signaling.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2171390&req=5

fig7: Calcium-independent microtubule-dependent pathway is required for FcɛRI-mediated degranulation in mast cells. The FcɛRI-mediated signaling pathway can be dissected into calcium-dependent and calcium-independent pathways. The calcium-independent pathway is critical for microtubule-dependent translocation of granules to the plasma membrane, and this pathway is regulated by Fyn/Gab2/RhoA signaling.
Mentions: The presence of a calcium-independent pathway was suggested previously by a study showing that Fyn-deficient BMMCs have an impaired FcɛRI-induced mast cell degranulation, but an intact calcium influx (Parravicini et al., 2002). Taking this and our findings together, we propose that the mast cell degranulation process can be dissected into two steps: the calcium-independent and microtubule-dependent process and the calcium-dependent one. The former step is involved in the translocation of granules to the plasma membrane, the latter involved in the fusion of granule with the plasma membrane and exocytosis (Fig. 7).

Bottom Line: Drugs affecting microtubule dynamics effectively suppressed the FcepsilonRI-mediated translocation of granules to the plasma membrane and degranulation.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.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Kanagawa 230-0045, Japan.

ABSTRACT
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.

Show MeSH