眼皮肤白化病是由于合成黑色素的黑素小体功能紊乱导致的遗传性疾病。溶酶体与黑素小体的互作对于黑素小体成熟具有重要作用。本研究的聚焦点是PI(3,5)P2通过调控黑素小体以及溶酶体内离子平衡进而调节溶酶体与黑素小体的互作。TPC2是被PI(3,5)P2激活的Na+/Ca2+离子通道, 可通过调节细胞器内的pH影响其互作。在本研究中，我们将1）利用细胞器膜片钳记录TPC2通道电流，同时利用荧光探针实时监测细胞器内腔的pH变化，研究溶酶体与黑素小体互作的分子机制；2）利用双转盘共聚焦显微镜、超分辨荧光显微镜以及免疫电镜技术等，研究PI(3,5)P2-TPC2调节溶酶体与黑素小体互作动态变化的细胞学机制。以上研究对于深入理解细胞器离子稳态对细胞器互作，细胞器发生及功能的影响具有普遍意义。利用电生理技术结合荧光成像解决离子流向问题，为研究细胞器离子稳态调节提供新的方法。

Oculocutaneous albinism (OCA) is a group of inherited disorders caused by dysfunction of melanosomes, where melanin is synthesized. Interaction between lysosome and melanosome is critical for biogenesis of melanosome. PI(3,5)P2（phosphatidylinositol 3,5-bisphosphate）plays a critical role in regulating lysosome and melanosome interaction. Two Pore Channel 2 (TPC2), gated by PI(3,5)P2, is a lysosome and melanosome localized, Na+/Ca2+ permeable cation channel, and involved in pH regulated inter-membrane interaction. In this proposal, 1) lysosome and melanosome patch clamping technique combined with fluorescent microscopy will be used to study the physiological and molecular mechanism of PI(3,5)P2-TPC2 axis in luminal pH regulation of lysosome and melanosome. 2) Two-spinning disc confocal, super-resolution and immuno-electoral microscopy will be used to study the cellular mechanism of PI(3,5)P2-TPC2 regulated lysosome and melanosome interaction. This study will be of significance in understanding the importance of organellar ion homeostasis in inter-membrane interaction, which is important for organellar biogenesis and function. The combination of electrophysiology and cell biology methods provides a unique way to study organellar ion homeostasis and interactions.