Rab46: a novel player in mast cell function
Rab46: a novel player in mast cell function
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Rab46：肥大细胞功能的新参与者
DOI：
10.1101/2023.03.13.532191
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Pedicini L
中科院分区：
文献类型：
--
作者：
Pedicini L
肥大细胞由于其快速释放储存在细胞质颗粒中的多种炎症介质的能力而因介导过敏性和炎症性疾病而臭名昭著。然而，肥大细胞还具有几种重要的生理作用，涉及这些活性介质的选择性和激动剂特异性释放。虽然在质膜的过滤机制可以调节一些货物的选择性释放，过多的存储货物和肥大细胞功能的多样性表明存在不同的运输途径的颗粒亚型。这些颗粒的差异运输和胞吐作用的分子机制尚不清楚，也不清楚颗粒运输如何与刺激相结合。在内皮细胞中，Rab46对组胺而不是凝血酶信号作出反应，并且这调节内皮特异性颗粒的亚群的运输。在这里，我们首次试图探索Rab46是否在肥大细胞功能中发挥作用。我们证明Rab46在人和鼠肥大细胞中高度表达，Rab46基因缺失对肥大细胞脱粒有影响，这取决于刺激和肥大细胞亚型。Rab46对肥大细胞功能的贡献以及Rab46在其他细胞类型中的刺激依赖性贩运中的作用的初步了解需要进一步研究Rab46在肥大细胞颗粒贩运中的作用，以便可以开发用于治疗肥大细胞介导的多种病理的新的和特异性的治疗靶点。
Mast cells are infamous for mediating allergic and inflammatory diseases due to their capacity of rapidly releasing a wide range of inflammatory mediators stored in cytoplasmic granules. However, mast cells also have several important physiological roles that involve selective and agonist-specific release of these active mediators. While a filtering mechanism at the plasma membrane could regulate the selective release of some cargo, the plethora of stored cargo and the diversity of mast cell functions suggests the existence of granule subtypes with distinct trafficking pathways. The molecular mechanisms underlying differential trafficking and exocytosis of these granules are not known, neither is it clear how granule trafficking is coupled to the stimulus. In endothelial cells, a Rab GTPase, Rab46, responds to histamine but not thrombin signals, and this regulates the trafficking of a subpopulation of endothelial-specific granules. Here, we sought to explore, for the first time, if Rab46 plays a role in mast cell function. We demonstrate that Rab46 is highly expressed in human and murine mast cells, and Rab46 genetic deletion has an effect on mast cell degranulation that depends on both stimuli and mast cell subtype. This initial insight into the contribution of Rab46 to mast cell function and the understanding of the role of Rab46 in stimuli-dependent trafficking in other cell types necessitates further investigations of Rab46 in mast cell granular trafficking so that novel and specific therapeutic targets for treatment of the diverse pathologies mediated by mast cells can be developed.
DOI：
10.1016/j.bbrc.2014.11.095
发表时间：
2015-01-02
影响因子：
3.1
作者：
Wilson, Lesley A.;McKeown, Lynn;Tumova, Sarka;Li, Jing;Beech, David J.
通讯作者：
Beech, David J.
影响因子：
15.9
作者：
Gaudenzio, Nicolas;Sibilano, Riccardo;Galli, Stephen J.
通讯作者：
Galli, Stephen J.