Differential regulation of mast cell degranulation versus cytokine secretion by the actin regulatory proteins Coronin1a and Coronin1b.
Differential regulation of mast cell degranulation versus cytokine secretion by the actin regulatory proteins Coronin1a and Coronin1b.
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DOI：
10.1084/jem.20101757
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发表时间：
2011-08-29
期刊：
影响因子：
--
通讯作者：
Bulfone-Paus S
中科院分区：
文献类型：
--
作者：
Föger N;Jenckel A;Orinska Z;Lee KH;Chan AC;Bulfone-Paus S
Coronin 1a通过肌动蛋白细胞骨架动力学抑制肥大细胞脱粒，同时增加细胞因子分泌，Coronin 1b的额外损失加剧了这种作用。肥大细胞（MC）通过高亲和力IgE受体（FcεRI）的聚集而活化，在涉及肌动蛋白细胞骨架重组的过程中引起脱粒和促炎介质的释放。然而，调节途径和细胞骨架变化和MC功能之间的分子联系还不完全清楚。在这项研究中，我们提供了肌动蛋白调节蛋白Coro 1a（Coro 1a）和Coro 1b在MCs胞外途径中的关键作用的遗传证据：Coro 1a −/−骨髓来源的MCs表现出Fcε RI介导的分泌溶酶体脱粒增加，但细胞因子分泌显著减少。Coro 1a −/− MCs的过度脱粒通过Coro 1b的额外损失而进一步增强。在体内，Coro 1a −/− Coro 1b −/−小鼠表现出增强的被动皮肤过敏反应。功能重建实验表明，Coro 1a对MC脱粒的抑制作用与Coro 1a的皮质定位密切相关，需要其丝状肌动蛋白结合活性，并受Coro 1a的Ser 2磷酸化的调节。因此，冠蛋白，反过来肌动蛋白细胞骨架，表现出功能二分法作为差异调节器的脱粒与细胞因子分泌在MC生物学。
Coronin1a inhibits mast cell degranulation through actin cytoskeletal dynamics while augmenting cytokine secretion, an effect exacerbated by additional loss of Coronin1b. Mast cell (MC) activation via aggregation of the high affinity IgE receptor (FcεRI) causes degranulation and release of proinflammatory mediators in a process that involves the reorganization of the actin cytoskeleton. However, the regulatory pathways and the molecular links between cytoskeletal changes and MC function are incompletely understood. In this study, we provide genetic evidence for a critical role of the actin-regulatory proteins Coronin1a (Coro1a) and Coro1b on exocytic pathways in MCs: Coro1a−/− bone marrow–derived MCs exhibit increased FcεRI-mediated degranulation of secretory lysosomes but significantly reduced secretion of cytokines. Hyperdegranulation of Coro1a−/− MCs is further augmented by the additional loss of Coro1b. In vivo, Coro1a−/−Coro1b−/− mice displayed enhanced passive cutaneous anaphylaxis. Functional reconstitution assays revealed that the inhibitory effect of Coro1a on MC degranulation strictly correlates with cortical localization of Coro1a, requires its filamentous actin–binding activity, and is regulated by phosphorylation of Ser2 of Coro1a. Thus, coronin proteins, and in turn the actin cytoskeleton, exhibit a functional dichotomy as differential regulators of degranulation versus cytokine secretion in MC biology.
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DOI：
10.1084/jem.20041891
发表时间：
2005-03-21
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Sasaki J;Sasaki T;Yamazaki M;Matsuoka K;Taya C;Shitara H;Takasuga S;Nishio M;Mizuno K;Wada T;Miyazaki H;Watanabe H;Iizuka R;Kubo S;Murata S;Chiba T;Maehama T;Hamada K;Kishimoto H;Frohman MA;Tanaka K;Penninger JM;Yonekawa H;Suzuki A;Kanaho Y
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DOI：
10.1016/j.bbamcr.2006.09.004
发表时间：
2006-11-01
影响因子：
5.1
作者：
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Gasman, Stephane
影响因子：
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3.3
作者：
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作者：
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