A melanosomal two-pore sodium channel regulates pigmentation.
A melanosomal two-pore sodium channel regulates pigmentation.
复制标题
DOI：
10.1038/srep26570
复制
发表时间：
2016-05-27
影响因子：
4.6
通讯作者：
Oancea E
中科院分区：
文献类型：
--
作者：
Bellono NW;Escobar IE;Oancea E
细胞内细胞器介导复杂的细胞功能，通常需要离子转运穿过它们的膜。黑素体是负责合成主要哺乳动物色素黑色素的细胞器。黑色素合成的缺陷导致色素沉着缺陷、视觉缺陷以及对皮肤癌和眼癌的易感性增加。虽然编码黑素体离子转运蛋白的基因已被确定为黑素合成的关键调节因子，但对黑素体离子转运及其对色素沉着的作用仍知之甚少。在这里，我们确定双孔通道2（TPC 2）作为第一个报告的黑素体阳离子电导直接膜片钳皮肤和眼睛黑素体。TPC 2与人类色素沉着和黑色素瘤有关，但介导这种功能的分子机制完全未知。我们证明了囊泡信号脂质磷脂酰肌醇二磷酸PI（3，5）P2调节TPC 2活性，以控制黑素体膜电位，pH值，并调节色素沉着。
Intracellular organelles mediate complex cellular functions that often require ion transport across their membranes. Melanosomes are organelles responsible for the synthesis of the major mammalian pigment melanin. Defects in melanin synthesis result in pigmentation defects, visual deficits, and increased susceptibility to skin and eye cancers. Although genes encoding putative melanosomal ion transporters have been identified as key regulators of melanin synthesis, melanosome ion transport and its contribution to pigmentation remain poorly understood. Here we identify two-pore channel 2 (TPC2) as the first reported melanosomal cation conductance by directly patch-clamping skin and eye melanosomes. TPC2 has been implicated in human pigmentation and melanoma, but the molecular mechanism mediating this function was entirely unknown. We demonstrate that the vesicular signaling lipid phosphatidylinositol bisphosphate PI(3,5)P2 modulates TPC2 activity to control melanosomal membrane potential, pH, and regulate pigmentation.