PDF(Pubmed)
Abstract：
α-synuclein (α-Syn) is a presynaptic protein that is involved in Parkinson\'s and other neurodegenerative diseases and binds to negatively charged phospholipids. Previously, we reported that α-Syn clusters synthetic proteoliposomes that mimic synaptic vesicles. This vesicle-clustering activity depends on a specific interaction of α-Syn with anionic phospholipids. Here, we report that α-Syn surprisingly also interacts with the neutral phospholipid lysophosphatidylcholine (lysoPC). Even in the absence of anionic lipids, lysoPC facilitates α-Syn-induced vesicle clustering but has no effect on Ca2+-triggered fusion in a single vesicle-vesicle fusion assay. The A30P mutant of α-Syn that causes familial Parkinson disease has a reduced affinity to lysoPC and does not induce vesicle clustering. Taken together, the α-Syn-lysoPC interaction may play a role in α-Syn function.
摘要：
α-突触核蛋白（α-Syn）是一种突触前蛋白，与帕金森氏病和其他神经退行性疾病有关，并与带负电荷的磷脂结合。以前,我们报道了α-Syn聚集模拟突触小泡的合成蛋白脂质体。这种囊泡聚集活性取决于α-Syn与阴离子磷脂的特定相互作用。这里,我们报道α-Syn令人惊讶地还与中性磷脂溶血磷脂酰胆碱(lysoPC)相互作用。即使在没有阴离子脂质的情况下，lysoPC促进α-Syn诱导的囊泡聚集，但在单个囊泡-囊泡融合分析中对Ca2触发的融合没有影响。导致家族性帕金森病的α-Syn的A30P突变体对lysoPC的亲和力降低,并且不诱导囊泡聚集。一起来看,α-Syn-lysoPC相互作用可能在α-Syn功能中起作用。
