An over-expression system for characterizing Ppt1 function in Drosophila.
An over-expression system for characterizing Ppt1 function in Drosophila.
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DOI：
10.1186/1471-2202-4-30
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发表时间：
2003-11-20
期刊：
影响因子：
2.4
通讯作者：
MacDonald ME
中科院分区：
文献类型：
--
作者：
Korey CA;MacDonald ME
婴儿期发病的神经元蜡质脂褐质沉积症 (INCL) 是最早也是最严重的 NCL 形式，其神经系统症状反映了中枢神经系统和视网膜的严重神经变性。 INCL 是由于 CLN1 位点隐性遗传突变所致。该基因座编码进化上保守的棕榈酰蛋白硫酯酶 1 (PPT1)，表明蛋白棕榈酰化在正常神经元功能中发挥着重要作用。为了开始阐明 Ppt1 在神经元细胞中发挥的具体作用，我们在果蝇中开发了 Ppt1 过表达系统。我们报告说，DmPpt1 在发育中的果蝇视觉系统中过度表达会导致细胞凋亡而损失。 DmPpt1 基因组缺陷会抑制这种 DmPpt1 过度表达表型。此外，具有催化位点丝氨酸123突变为丙氨酸的DmPpt1S123A的过度表达不会导致野生型DmPpt1过度表达所观察到的严重眼部表型。因此，DmPpt1 果蝇中的细胞损失与野生型 DmPpt1 的剂量直接相关。虽然INCL是因为PPT1丢失； DmPpt1 水平升高还可能通过对 PPT1 正常功能的某些方面产生有害影响而导致神经变性。这表明 PPT1 活性的精确水平对于神经元细胞的存活很重要。果蝇 DmPpt1 过表达系统为遗传实验提供了资源，旨在确定 PPT1 调节其必需蛋白质底物棕榈酰化状态的过程。
The infantile onset form of Neuronal Ceroid Lipofuscinoses (INCL) is the earliest and most severe form of NCL, with neurological symptoms that reflect massive neurodegeneration in the CNS and retina. INCL is due to recessively inherited mutations at the CLN1 locus. This locus encodes the evolutionarily conserved enzyme palmitoyl-protein thioesterase 1 (PPT1), indicating an essential role for protein palmitoylation in normal neuronal function. To begin to elucidate the specific role that Ppt1 plays in neuronal cells, we have developed a Ppt1 over-expression system in Drosophila. We report that over-expression of DmPpt1 in the developing Drosophila visual system leads to the loss of cells through apoptotic cell death. This DmPpt1 over-expression phenotype is suppressed by DmPpt1 genomic deficiencies. Moreover, over-expression of DmPpt1S123A, which bears a catalytic site serine 123 to alanine mutation, does not lead to the severe eye phenotype observed with over-expression of wild-type DmPpt1. Thus, cell loss in DmPpt1 flies is directly related to the dosage of wildtype DmPpt1. Although INCL is due to the loss of PPT1; increased levels of DmPpt1 also lead to neurodegeneration possibly via a detrimental effect on some aspect of PPT1's normal function. This suggests that the precise levels of PPT1 activity are important for neuronal cell survival. The Drosophila DmPpt1 over-expression system provides a resource for genetic experiments that aim to identify the processes by which PPT1 regulates the palmitoylation-state of its essential protein substrates.
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影响因子：
11.4
作者：
Hellsten, E;Vesa, J;Peltonen, L
通讯作者：
Peltonen, L
影响因子：
3.5
作者：
Lehtovirta, M;Kyttälä, A;Jalanko, A
通讯作者：
Jalanko, A
影响因子：
64.5
作者：
Freeman, M
通讯作者：
Freeman, M
DOI：
10.1073/pnas.251485198
发表时间：
2001-11-20
影响因子：
11.1
作者：
Gupta, P;Soyombo, AA;Hofmann, SL
通讯作者：
Hofmann, SL
影响因子：
4.7
作者：
Cho, SG;Dawson, G
通讯作者：
Dawson, G