Palmitoyl protein thioesterase (PPT) localizes into synaptosomes and synaptic vesicles in neurons:: implications for infantile neuronal ceroid lipofuscinosis (INCL)
Palmitoyl protein thioesterase (PPT) localizes into synaptosomes and synaptic vesicles in neurons:: implications for infantile neuronal ceroid lipofuscinosis (INCL)
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DOI：
10.1093/hmg/10.1.69
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发表时间：
2001-01-01
影响因子：
3.5
通讯作者：
Jalanko, A
中科院分区：
文献类型：
--
作者：
Lehtovirta, M;Kyttälä, A;Jalanko, A
棕榈酰蛋白硫酯酶（PPT）的缺乏导致神经退行性疾病婴儿神经元蜡样质脂褐质沉积症（INCL），其特征在于皮质神经元几乎完全丧失。在COS-1细胞中表达的PPT被甘露糖-6-磷酸受体（M6 PR）识别并被路由到溶酶体，但PPT的大部分被分泌。我们在这里确定了PPT的神经元定位共聚焦显微镜，冷冻免疫电镜和细胞分级。在小鼠原代神经元和脑组织中，PPT定位于突触体和突触囊泡中，但不在溶酶体中。此外，在极化的上皮Caco-2细胞中，PPT仅定位于基底外侧位点，而与经典的溶酶体酶-乙酰氨基葡萄糖苷酶（阿加）相反，其定位于顶端位点。目前的数据表明，PPT在大脑中的溶酶体外发挥作用，可能与突触功能有关。这一发现为研究INCL相关的神经病理学事件提供了一条新的途径。
A deficiency of palmitoyl protein thioesterase (PPT) leads to the neurodegenerative disease infantile neuronal ceroid lipofuscinosis (INCL), which is characterized by an almost complete loss of cortical neurons. PPT expressed in COS-1 cells is recognized by the mannose-6-phosphate receptor (M6PR) and is routed to lysosome, but a substantial fraction of PPT is secreted. We have here determined the neuronal localization of PPT by confocal microscopy, cryoimmunoelectron microscopy and cell fractionation. In mouse primary neurons and brain tissue, PPT is localized in synaptosomes and synaptic vesicles but not in lysosomes, Furthermore, in polarized epithelial Caco-2 cells, PPT is localized exclusively to the basolateral site, in contrast to the classical lysosomal enzyme, aspartylglucosaminidase (AGA), which is localized in the apical site. The current data imply that PPT has a role outside the lysosomes in the brain and may be associated with synaptic functioning. This finding operas a new route to study the neuropathological events associated with INCL.