Doktór Bartosz, Damulewicz Milena, Krzeptowski Wojciech, Bednarczyk Barbara, Pyza Elżbieta Małgorzata
Department of Cell Biology and Imaging, Institute of Zoology and Biomedical Research, Jagiellonian University, Kraków, Poland.
Department of Cell Biology and Imaging, Institute of Zoology and Biomedical Research, Jagiellonian University, Kraków, Poland;
Acta Neurobiol Exp (Wars). 2018;78(3):231-241.
Mutations in the PINK1 gene are responsible for typical symptoms of Parkinson's disease. Using Drosophila melanogaster mutant PINK1B9 and after PINK1 silencing with RNAi using transgenic lines, we observed defects in synapses and behavior. The lack or reduced expression of PINK1 prolonged sleep during the day (nap) and decreased the total locomotor activity during 24 h, in addition to a decrease in climbing ability and a reduced lifespan. In the brain, PINK1 mutants had a lower level of Bruchpilot (BRP), a presynaptic scaffolding protein that is crucial for neurotransmission in all type of synapses in Drosophila. In addition, other proteins that are involved in synaptic transmission; Rab5, Syntaxin and Wishful Thinking were also decreased in abundance in mutants, except Synaptotagmin. Transmission electron microscopy (TEM) also confirmed less and abnormal synaptic vesicles at tetrad synapses in the visual system of PINK1 mutants. The lower level of BRP and longer day sleep observed was also detected in white mutants, which were examined to test the effect of the\r\nwhite background on the PINK1B9 strain. The reduced locomotor activity and longer day sleep in PINK1 mutants and after decreasing the PINK1 level in neurons seem to be correlated with a decrease in mitochondria number during the day, when they normally peak, and with impaired synaptic transmission.
PINK1基因的突变是帕金森病典型症状的成因。利用果蝇突变体PINK1B9，并通过转基因品系使用RNAi使PINK1沉默后，我们观察到了突触和行为方面的缺陷。PINK1的缺失或表达减少会延长白天的睡眠时间（午睡），并降低24小时内的总运动活性，此外还会导致攀爬能力下降和寿命缩短。在大脑中，PINK1突变体中Bruchpilot（BRP）的水平较低，BRP是一种突触前支架蛋白，对果蝇所有类型突触中的神经传递至关重要。此外，参与突触传递的其他蛋白质；Rab5、Syntaxin和Wishful Thinking在突变体中的丰度也降低了，但突触结合蛋白除外。透射电子显微镜（TEM）也证实，PINK1突变体视觉系统中四联突触处的突触小泡数量减少且异常。在白色突变体中也检测到了较低水平的BRP和较长的白天睡眠时间，对其进行检测以测试白色背景对PINK1B9品系的影响。PINK1突变体以及神经元中PINK1水平降低后运动活性降低和白天睡眠时间延长，似乎与白天线粒体数量减少（正常情况下白天线粒体数量达到峰值）以及突触传递受损有关。
