Presenilin is required for proper morphology and function of neurons in C. elegans
Presenilin is required for proper morphology and function of neurons in C. elegans
复制标题
早老素是线虫神经元正常形态和功能所必需的
DOI：
10.1038/35018575
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发表时间：
2000
期刊：
影响因子：
64.8
通讯作者：
R. Baumeister
中科院分区：
文献类型：
--
作者：
N. Wittenburg;S. Eimer;B. Lakowski;Sascha Röhrig;C. Rudolph;R. Baumeister
人类早老素基因的突变导致家族性阿尔茨海默病（FAD）的最常见和侵袭性形式。本研究表明，除了在非神经元组织中决定细胞命运的作用外，早老素活性在体内终末分化的神经元中也是必需的。秀丽隐杆线虫早老素基因self -12和hop-1的突变导致动物温度记忆的缺陷。这种缺陷是由早老素突变体中两个胆碱能中间神经元的功能丧失引起的，这些神经元表现出神经突形态缺陷。通过在这些细胞中表达self -12，可以恢复self -12突变动物受损神经元的形态和功能。野生型人早老素PS1，而FAD突变体PS1 A246E，也能挽救这些形态缺陷。由于lin-12突变动物表现出与早老素突变体相似的形态和功能缺陷，我们认为早老素通过促进Notch信号传导介导其在有丝分裂后神经元中的活性。这些数据表明早老素对神经形态和功能的细胞自主和进化保守控制。
Mutations in the human presenilin genes cause the most frequent and aggressive forms of familial Alzheimer's disease (FAD). Here we show that in addition to its role in cell fate decisions in non-neuronal tissues, presenilin activity is required in terminally differentiated neurons in vivo. Mutations in the Caenorhabditis elegans presenilin genes sel-12 and hop-1 result in a defect in the temperature memory of the animals. This defect is caused by the loss of presenilin function in two cholinergic interneurons that display neurite morphology defects in presenilin mutants. The morphology and function of the affected neurons in sel-12 mutant animals can be restored by expressing sel-12 only in these cells. The wild-type human presenilin PS1, but not the FAD mutant PS1 A246E, can also rescue these morphological defects. As lin-12 mutant animals display similar morphological and functional defects to presenilin mutants, we suggest that presenilins mediate their activity in postmitotic neurons by facilitating Notch signalling. These data indicate cell-autonomous and evolutionarily conserved control of neural morphology and function by presenilins.
影响因子：
56.9
作者：
Sestan, N;Artavanis-Tsakonas, S;Rakic, P
通讯作者：
Rakic, P
DOI：
10.1073/pnas.94.7.3384
发表时间：
1997-04-01
影响因子：
11.1
作者：
Yu, S;Avery, L;Garbers, DL
通讯作者：
Garbers, DL