Division of Experimental Pneumology, Research Center Borstel, Leibniz Lungenzentrum, Airway Research Center North, German Center for Lung Research (DZL), Borstel, Germany.
Department of Signal Transduction, Institute of Molecular Genetics of the Czech Academy of Sciences, Prague, Czech Republic.
Med Microbiol Immunol. 2020 Aug;209(4):531-543. doi: 10.1007/s00430-020-00679-x. Epub 2020 Jun 7.
Mast cells (MCs) are long-living immune cells highly specialized in the storage and release of different biologically active compounds and are involved in the regulation of innate and adaptive immunity. MC degranulation and replacement of MC granules are accompanied by active membrane remodelling. Tetraspanins represent an evolutionary conserved family of transmembrane proteins. By interacting with lipids and other membrane and intracellular proteins, they are involved in organisation of membrane protein complexes and act as "molecular facilitators" connecting extracellular and cytoplasmic signaling elements. MCs express different tetraspanins and MC degranulation is accompanied by changes in membrane organisation. Therefore, tetraspanins are very likely involved in the regulation of MC exocytosis and membrane reorganisation after degranulation. Antiviral response and production of exosomes are further aspects of MC function characterized by dynamic changes of membrane organization. In this review, we pay a particular attention to tetraspanin gene expression in different human and murine MC populations, discuss tetraspanin involvement in regulation of key MC signaling complexes, and analyze the potential contribution of tetraspanins to MC antiviral response and exosome production. In-depth knowledge of tetraspanin-mediated molecular mechanisms involved in different aspects of the regulation of MC response will be beneficial for patients with allergies, characterized by overwhelming MC reactions.
肥大细胞 (MCs) 是具有长寿命的免疫细胞，高度特化于储存和释放不同的生物活性化合物，并参与先天和适应性免疫的调节。MC 脱颗粒和 MC 颗粒的替换伴随着活跃的膜重塑。四跨膜蛋白是一个进化上保守的跨膜蛋白家族。通过与脂质和其他膜及细胞内蛋白相互作用，它们参与膜蛋白复合物的组织，并作为“分子促进剂”连接细胞外和细胞质信号元件。MC 表达不同的四跨膜蛋白，MC 脱颗粒伴随着膜组织的变化。因此，四跨膜蛋白很可能参与调节 MC 脱颗粒后的胞吐作用和膜重组。抗病毒反应和外泌体的产生是 MC 功能的另一个方面，其特征是膜组织的动态变化。在这篇综述中，我们特别关注不同人类和鼠类 MC 群体中四跨膜蛋白基因的表达，讨论四跨膜蛋白在调节关键 MC 信号复合物中的作用，并分析四跨膜蛋白对 MC 抗病毒反应和外泌体产生的潜在贡献。深入了解四跨膜蛋白介导的分子机制，参与 MC 反应调节的不同方面，将有利于过敏患者，其特征是 MC 反应过度。
