P2X7 receptor regulation of non-classical secretion from immune effector cells.
P2X7 receptor regulation of non-classical secretion from immune effector cells.
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DOI：
10.1111/cmi.12001
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发表时间：
2012-11
影响因子：
3.4
通讯作者：
Dubyak GR
中科院分区：
文献类型：
--
作者：
Dubyak GR
P2X7 受体 (P2X7R) 是在免疫效应细胞中表达的细胞外 ATP 门控离子通道，在微生物感染或急性组织创伤的早期阶段执行关键的保护反应。 P2X7R 阳性细胞包括单核细胞、巨噬细胞、树突状细胞和 T 细胞。鉴于 ATP 存在于所有宿主和病原体细胞类型中，ATP 可以很容易地释放到组织损伤和微生物入侵局部部位的细胞外区室中。因此，细胞外 ATP 及其宿主效应细胞上的靶受体可被视为先天免疫系统的附加要素。在这方面，刺激 P2X7R 迅速触发炎症反应的关键步骤：诱导 NLRP3/caspase-1 炎症信号复合物，驱动促炎细胞因子白细胞介素 1β (IL-1β) 和白细胞介素 18 (IL-18) 的蛋白水解成熟和分泌。 IL-1β（和 IL-18）缺乏在高尔基体和经典分泌囊泡内划分的信号序列，并且 proIL-1β 前体在游离核糖体上翻译后在胞浆内积累。因此，ATP 诱导的成熟 IL-1β 细胞因子在细胞外区室中的积累需要从胞质区室输出的非经典机制。提出的五种机制包括：1）分泌性溶酶体的胞吐作用，通过未定义的蛋白质转运蛋白积累胞质 IL-1β； 2) 释放膜界定的微泡，这些微泡源自质膜泡，这些泡由表面膜的外凸形成，捕获胞质IL-β； 3) 膜界定的外泌体的释放继发于多囊泡体的胞吐作用，该多囊泡体是由捕获胞质IL-β的再循环内体的内陷形成的； 4)自噬体或自噬溶酶体的胞吐作用，在初始自噬隔离膜或omegasome形成过程中通过包埋积累胞质IL-1β； 5) 细胞焦亡或坏死性凋亡继发调节细胞死亡后直接释放胞质 IL-1β。这些机制并不相互排斥，可能代表平行或交叉的膜运输反应对 P2X7 受体激活的参与。
P2X7 receptors (P2X7R) are extracellular ATP-gated ion channels expressed in the immune effector cells that carry out critical protective responses during the early phases of microbial infection or acute tissue trauma. P2X7R-positive cells include monocytes, macrophages, dendritric cells, and T-cells. Given its presence in all host and pathogen cell types, ATP can be readily released into extracellular compartments at local sites of tissue damage and microbial invasion. Thus, extracellular ATP and its target receptors on host effector cells can be considered as additional elements of the innate immune system. In this regard, stimulation of P2X7R rapidly triggers a key step of the inflammatory response: induction of NLRP3/caspase-1 inflammasome signaling complexes that drive the proteolytic maturation and secretion of the proinflammatory cytokines interleukin-1β(IL-1β) and interleukin-18 (IL-18). IL-1β(and IL-18) lacks a signal sequence for compartmentation within the Golgi and classical secretory vesicles and the proIL-1β precursor accumulates within the cytosol following translation on free ribosomes. Thus, ATP-induced accumulation of the mature IL-1β cytokine within extracellular compartments requires non-classical mechanisms of export from the cytosolic compartment. Five proposed mechanisms include: 1) exocytosis of secretory lysosomes that accumulate cytosolic IL-1β via undefined protein transporters; 2) release of membrane-delimited microvesicles derived from plasma membrane blebs formed by evaginations of the surface membrane that entrap cytosolic IL-β; 3) release of membrane-delimited exosomes secondary to the exocytosis of multivesicular bodies formed by invaginations of recycling endosomes that entrap cytosolic IL-β; 4) exocytosis of autophagosomes or autophagolysosomes that accumulate cytosolic IL-1β via entrapment during formation of the initial autophagic isolation membrane or omegasome; and 5) direct release of cytosolic IL-1β secondary to regulated cell death by pyroptosis or necroptosis. These mechanisms are not mutually exclusive and may represent engagement of parallel or intersecting membrane trafficking responses to P2X7 receptor activation.
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影响因子：
64.5
作者：
Gurcel, Laure;Abrami, Laurence;van der Goot, F. Gisou
通讯作者：
van der Goot, F. Gisou
影响因子：
5.5
作者：
Gudipaty, L;Munetz, J;Dubyak, GR
通讯作者：
Dubyak, GR
DOI：
10.1038/nri2938
发表时间：
2011-03
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
通讯作者：
--
影响因子：
4.8
作者：
Harris, James;Hartman, Michelle;Lavelle, Ed C.
通讯作者：
Lavelle, Ed C.
影响因子：
11.4
作者：
Bianco, Fabio;Perrotta, Cristiana;Novellino, Luisa;Francolini, Maura;Riganti, Loredana;Menna, Elisabetta;Saglietti, Laura;Schuchman, Edward H.;Furlan, Roberto;Clementi, Emilio;Matteoli, Michela;Verderio, Claudia
通讯作者：
Verderio, Claudia