Redefining the concept of protease-activated receptors: cathepsin S evokes itch via activation of Mrgprs.
Redefining the concept of protease-activated receptors: cathepsin S evokes itch via activation of Mrgprs.
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DOI：
10.1038/ncomms8864
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发表时间：
2015-07-28
影响因子：
16.6
通讯作者：
Lerner EA
中科院分区：
文献类型：
--
作者：
Reddy VB;Sun S;Azimi E;Elmariah SB;Dong X;Lerner EA
表达Mas-related G蛋白偶联受体（Mrs 11）的感觉神经元介导组胺非依赖性瘙痒。我们发现，半胱氨酸蛋白酶组织蛋白酶S激活MrgprC 11和唤起受体依赖性抓挠小鼠。与其常规蛋白酶激活受体的激活相反，组织蛋白酶S介导的MrgprC 11的激活不涉及栓系配体的产生。我们进一步证明，不同的半胱氨酸蛋白酶选择性地激活特定的小鼠和人类MrGPR家族成员。我们对蛋白酶与GPCR相互作用的理解的扩展重新定义了什么构成蛋白酶激活受体的概念。这些发现还暗示蛋白酶是这个孤儿受体家族成员的配体，同时为半胱氨酸蛋白酶如何促进瘙痒提供了新的见解。
Sensory neurons expressing Mas-related G protein coupled receptors (Mrgprs) mediate histamine-independent itch. We show that the cysteine protease cathepsin S activates MrgprC11 and evokes receptor-dependent scratching in mice. In contrast to its activation of conventional protease-activated receptors, cathepsin S mediated activation of MrgprC11 did not involve the generation of a tethered ligand. We demonstrate further that different cysteine proteases selectively activate specific mouse and human Mrgpr family members. This expansion of our understanding by which proteases interact with GPCRs redefines the concept of what constitutes a protease-activated receptor. The findings also implicate proteases as ligands to members of this orphan receptor family while providing new insights into how cysteine proteases contribute to itch.