Presenilin PS1∆E9 disrupts mobility of secretory organelles in rat astrocytes.
Presenilin PS1∆E9 disrupts mobility of secretory organelles in rat astrocytes.
复制标题
DOI：
10.1111/apha.13046
复制
发表时间：
2018-06
期刊：
影响因子：
--
通讯作者：
Zorec R
中科院分区：
文献类型：
--
作者：
Stenovec M;Trkov Bobnar S;Smolič T;Kreft M;Parpura V;Zorec R
阿尔茨海默病（AD）主要被认为是一种神经元源性损伤，但也涉及星形胶质细胞的衰竭。最近的一项研究表明，突变的早老素1（PS1 M146 V），一个假定的内质网（ER）的钙离子通道，降低钙离子电导，损害交通的星形胶质细胞肽能囊泡。其他致病相关的PS1突变体，如PS1ΔE9，编码ER通道，具有假定的Ca 2+电导增加，是否同样影响囊泡运输，尚不清楚。在这里，我们将编码突变型PS1ΔE9和心房利钠肽或囊泡谷氨酸转运蛋白1的质粒与荧光蛋白标记的质粒共转染大鼠星形胶质细胞，（分别为pANP.emd或pVGLUT 1-EGFP），以显微镜检查囊泡移动性和神经胶质信号传导分子的Ca 2+调节释放的改变是否表现为一般的基于囊泡的缺陷;转染对照细胞以共表达外源或天然野生型PS1和pANP.emd或pVGLUT 1-EGFP。在静息时和增加细胞内钙活性的ATP刺激后分析囊泡的移动性。在PS1ΔE9星形胶质细胞中，与对照组相比，两种囊泡类型的自发运动性降低（P<0.001）。在PS1ΔE9星形胶质细胞中，快速囊泡运动的刺激后恢复受到阻碍。与对照组相比，PS 1 ΔE9星形胶质细胞中ATP诱导的肽释放效率较低（P<0.05），这些囊泡的预刺激移动性也较低。尽管PS1突变体PS1 M146 V和PS1ΔE9对ER Ca 2+电导的影响不同，但我们的结果揭示了PS1ΔE9星形胶质细胞中常见的囊泡型无选择性运输缺陷，表明减少的基于分泌囊泡的信号传导是AD星形胶质细胞的普遍缺陷。
Alzheimer disease (AD) is largely considered a neuron-derived insult, but also involves failure of astroglia. A recent study indicated that mutated presenilin 1 (PS1M146V), a putative endoplasmic reticulum (ER) Ca2+ channel with decreased Ca2+ conductance, impairs the traffic of astroglial peptidergic vesicles. Whether other pathogenically relevant PS1 mutants, such as PS1ΔE9, which code for ER channel with putative increased Ca2+ conductance, similarly affect vesicle traffic, is unknown. Here, we co-transfected rat astrocytes with plasmids encoding mutant PS1ΔE9 and atrial natriuretic peptide or vesicular glutamate transporter 1 tagged with fluorescent proteins (pANP.emd or pVGLUT1-EGFP, respectively), to microscopically examine whether alterations in vesicle mobility and Ca2+-regulated release of gliosignalling molecules manifest as a general vesicle-based defect; control cells were transfected to co-express exogenous or native wild-type PS1 and pANP.emd or pVGLUT1-EGFP. The vesicle mobility was analyzed at rest and after ATP stimulation that increased intracellular calcium activity. In PS1ΔE9 astrocytes, spontaneous mobility of both vesicle types was reduced (P<0.001) when compared to controls. Post-stimulatory recovery of fast vesicle mobility was hampered in PS1ΔE9 astrocytes. The ATP-evoked peptide release was less efficient in PS1ΔE9 astrocytes than in the controls (P<0.05), as was the pre-stimulatory mobility of these vesicles. Although the PS1 mutants PS1M146V and PS1ΔE9 differently affect ER Ca2+ conductance, our results revealed a common, vesicle type indiscriminate trafficking defect in PS1ΔE9 astrocytes, indicating that reduced secretory vesicle-based signalling is a general deficit in AD astrocytes.
登录
查看更多内容
DOI：
10.1016/j.bbrc.2012.10.082
发表时间：
2012-11-30
影响因子：
3.1
作者：
de Diego, Antonio M. G.;Lorrio, Silvia;Garcia, Antonio G.
通讯作者：
Garcia, Antonio G.
影响因子：
8
作者：
Gucek, Alenka;Jorgacevski, Jernej;Zorec, Robert
通讯作者：
Zorec, Robert
影响因子：
64.8
作者：
De Strooper, B;Saftig, P;Van Leuven, F
通讯作者：
Van Leuven, F
影响因子：
3.5
作者：
Gunawardena, Shermali;Yang, Ge;Goldstein, Lawrence S. B.
通讯作者：
Goldstein, Lawrence S. B.
影响因子：
15.1
作者：
Olabarria M;Noristani HN;Verkhratsky A;Rodríguez JJ
通讯作者：
Rodríguez JJ