Research on molecular function of ATP13A2 and neuronal cell death causing altered localization of ATP13A2

ATP13A2是家族性帕金森病(PARK9)的致病基因产物之一，定位于溶酶体膜。抑制ATP13A2表达可诱导SH-SY5Y细胞发生凋亡。表达缺陷的SH-SY5Y细胞中组织蛋白酶尤其是组织蛋白酶D的活性增加。此外，电子显微镜下可见SH-SY5Y细胞中可与LAMP2和组织蛋白酶D抗体免疫反应的高密度大结构。这些数据表明，由ATP13A2功能丧失引起的PARK9与溶酶体功能障碍有关，从而导致细胞死亡。

ATP13A2, identified as one of the causative gene product for familial parkinson's disease (PARK9), localized at lysosomal membrane. The suppression of ATP13A2 expression led to apoptosis in SH-SY5Y cells. The defective expression also was increased an enzyme activity of cathepsins, especially cathepsin D. Moreover, electron microscopy showed the accumulation of high density large structure, which was immunoreacted with antibodies against lamp2 and cathepsin D, in SH-SY5Y cells. These data suggests that PARK9 caused by loss-of-function of ATP13A2 is associated with lysosomal dysfunction, resulting in cell death.