Pirt是一种磷酸肌醇结合蛋白，作为TRPV1的调节亚基发挥作用。
Pirt, a phosphoinositide-binding protein, functions as a regulatory subunit of TRPV1.
作者信息
Kim Andrew Y, Tang Zongxiang, Liu Qin, Patel Kush N, Maag David, Geng Yixun, Dong Xinzhong
机构信息
The Solomon H. Snyder Department of Neuroscience, Center for Sensory Biology, School of Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
出版信息
Cell. 2008 May 2;133(3):475-85. doi: 10.1016/j.cell.2008.02.053.
Transient receptor potential vanilloid 1 (TRPV1) is a molecular sensor of noxious heat and capsaicin. Its channel activity can be modulated by several mechanisms. Here we identify a membrane protein, Pirt, as a regulator of TRPV1. Pirt is expressed in most nociceptive neurons in the dorsal root ganglia (DRG) including TRPV1-positive cells. Pirt null mice show impaired responsiveness to noxious heat and capsaicin. Noxious heat- and capsaicin-sensitive currents in Pirt-deficient DRG neurons are significantly attenuated. Heterologous expression of Pirt strongly enhances TRPV1-mediated currents. Furthermore, the C terminus of Pirt binds to TRPV1 and several phosphoinositides, including phosphatidylinositol-4,5-bisphosphate (PIP2), and can potentiate TRPV1. The PIP2 binding is dependent on the cluster of basic residues in the Pirt C terminus and is crucial for Pirt regulation of TRPV1. Importantly, the enhancement of TRPV1 by PIP2 requires Pirt. Therefore, Pirt is a key component of the TRPV1 complex and positively regulates TRPV1 activity.
瞬时受体电位香草酸亚型1（TRPV1）是一种有害热和辣椒素的分子传感器。其通道活性可通过多种机制进行调节。在此，我们鉴定出一种膜蛋白Pirt作为TRPV1的调节因子。Pirt在背根神经节（DRG）的大多数伤害性神经元中表达，包括TRPV1阳性细胞。Pirt基因敲除小鼠对有害热和辣椒素的反应性受损。Pirt缺陷型DRG神经元中对有害热和辣椒素敏感的电流显著减弱。Pirt的异源表达强烈增强TRPV1介导的电流。此外，Pirt的C末端与TRPV1以及几种磷酸肌醇结合，包括磷脂酰肌醇-4,5-二磷酸（PIP2），并且可以增强TRPV1。PIP2结合依赖于Pirt C末端的碱性残基簇，并且对于Pirt对TRPV1的调节至关重要。重要的是，PIP2对TRPV1的增强作用需要Pirt。因此，Pirt是TRPV1复合物的关键组成部分，并正向调节TRPV1活性。
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