Fc{epsilon}RI-mediated mast cell degranulation requires calcium-independent microtubule-dependent translocation of granules to the plasma membrane.
Fc{epsilon}RI-mediated mast cell degranulation requires calcium-independent microtubule-dependent translocation of granules to the plasma membrane.
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DOI：
10.1083/jcb.200501111
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发表时间：
2005-07-04
期刊：
影响因子：
--
通讯作者：
Hirano T
中科院分区：
文献类型：
--
作者：
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
高亲和性IgE受体（Fc受体I [Fc]）在肥大细胞上的聚集是胞质颗粒释放炎症和过敏介质的有力刺激。然而，脱粒的分子机制尚未确定。目前尚不清楚Fc i介导的信号转导最终如何调节细胞骨架的重组以及这些事件如何导致脱颗粒。在这里，我们证明了Fc / RI刺激以一种独立于钙的方式触发微管的形成。影响微管动力学的药物有效地抑制了Fc / ri介导的颗粒向质膜的转运和脱粒。此外，颗粒向质膜的移位与钙无关，但介质的释放和颗粒与质膜的融合完全依赖于钙。因此，脱粒过程可以分解为两个事件：钙依赖性微管依赖性颗粒向质膜的移位和钙依赖性膜融合和胞吐。最后，我们发现Fyn/Gab2/RhoA信号通路（而不是Lyn/SLP-76）在钙非依赖性微管依赖通路中起关键作用。
The aggregation of high affinity IgE receptors (Fcɛ receptor I [FcɛRI]) 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 FcɛRI-mediated signal transduction ultimately regulates the reorganization of the cytoskeleton and how these events lead to degranulation. Here, we show that FcɛRI stimulation triggers the formation of microtubules in a manner independent of calcium. Drugs affecting microtubule dynamics effectively suppressed the FcɛRI-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.
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DOI：
10.1084/jem.20021806
发表时间：
2003-06-02
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Gonzalez-Espinosa C;Odom S;Olivera A;Hobson JP;Martinez ME;Oliveira-Dos-Santos A;Barra L;Spiegel S;Penninger JM;Rivera J
通讯作者：
Rivera J
DOI：
10.1084/jem.190.10.1527
发表时间：
1999-11-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Cao MY;Davidson D;Yu J;Latour S;Veillette A
通讯作者：
Veillette A
影响因子：
3.5
作者：
CHEEK, TR;BURGOYNE, RD
通讯作者：
BURGOYNE, RD
影响因子：
4.4
作者：
Goitsuka, R;Kanazashi, H;Kitamura, D
通讯作者：
Kitamura, D
影响因子：
15.3
作者：
Hata, D;Kawakami, Y;Inagaki, N;Lantz, CS;Kitamura, T;Khan, WN;Maeda-Yamamoto, M;Miura, T;Han, W;Hartman, SE;Yao, L;Nagai, H;Goldfeld, AE;Alt, FW;Galli, SJ;Witte, ON;Kawakami, T
通讯作者：
Kawakami, T