紫外线为多种色素障碍性皮肤病的主要病因或诱因。目前关于紫外线诱发表皮生物学变化的上游机制了解甚少。我们前期发现目前唯一已知的眼外光通道蛋白——瞬时受体电位A1（TRPA1) 在角质形成细胞中亦有表达；且紫外线通过该通道参与调节细胞钙稳态及胞吞作用。本研究拟采用膜片钳及荧光探针技术，分析紫外线通过TRPA1通道对黑素细胞及角质形成细胞膜光电流及钙稳态影响；构建TRPA1突变体，确定脂膜信号PIP2与TRPA1作用位点；构建黑素小体钙离子及pH指示剂，了解TRPA1对黑素小体腔内钙稳态、pH及黑素合成影响；明确TRPA1与微管结合蛋白CYLD动态结合在黑素小体转运中动力学机制；建立TRPA1条件性基因敲除鼠等动物模型，明确体内机制、筛选有效药物。本研究预期结果将对深入了解紫外线相关色素障碍性皮肤病的光生物学发病机制、开发以TRPA1通路为靶向的、针对发病始动环节的预防及治疗药物具有重要意义。

Ultraviolet (UV) is the main pathogenesis or predisposing factors of pigmented dermatosis. Up to now, there is a little understanding of the upstream mechanisms of UV-induced epidermal biology. Recently, we found that transient receptor potential A1 (TRPA1) pathway , the only known extraocular phototransduction pathway in keratinocytes，and UV involved in the regulation of intracellular calcium homeostasis and endocytosis through the TRPA1 ion channels. In this study, we will analyze the effects of UV on the photocurrent and calcium homeostasis in melanocytes and keratinocytes through TRPA1 ion channels by patch clamp and fluorescence probe, determine the interaction sites of membrane signal PIP2 and TRPA1 by TRPA1 mutants, investigate the effects of TRPA1 pathway on the calcium homeostasis, pH of melanosome and melanin synthesis. We will construct melanosome-localized Ca2+ sensor and pH sensor to detect calcium concentration and pH changes in the melanosome lumen of living cells. Moreover, we will study dynamic mechanism of the dynamic binding of TRPA1 to microtubule-binding protein CYLD in melanosome transport. We will setup conditional TRPA1 knockout mice models to observe the effects of TRPA1 pathway in vivo and screen operative medicine. The expected results of this study will has great significance in understanding photobiological pathogenesis of pigmented dermatosis，and in development of TRPA1-targeted drugs for prevention and treatment by acting on initial step of disease.