Fragile x mental retardation 1 and filamin a interact genetically in Drosophila long-term memory.
Fragile x mental retardation 1 and filamin a interact genetically in Drosophila long-term memory.
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DOI：
10.3389/neuro.04.022.2009
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发表时间：
2010
影响因子：
3.5
通讯作者：
Tully T
中科院分区：
文献类型：
--
作者：
Bolduc FV;Bell K;Rosenfelt C;Cox H;Tully T
在过去的十年里，人们已经发现了与大量精神发育迟滞综合征相关的单基因缺陷。例如，脆性X综合征是智力迟钝的最常见原因，它是由FMR 1基因破坏引起的。类似地，脑室周围结节性异位症，包括脑畸形、癫痫和认知障碍，源于细丝蛋白A基因的破坏。虽然目前尚不清楚是否共同的分子途径的缺陷可能是这些各种综合征的认知功能障碍的基础，但细胞骨架结构的缺陷似乎是常见的几种精神发育迟滞综合征。已知FMR 1与Rac、profilin、PAK和Ras相互作用，其与树突棘缺陷相关。在果蝇中，dFmr 1基因的破坏会损害长期记忆（LTM），而细丝蛋白A同源物（cheerio）在LTM突变体的行为筛选中被鉴定出来。因此，我们研究了果蝇LTM形成过程中cheerio和dFmr 1之间可能的相互作用。我们发现，LTM具体是缺陷的dFmr 1/cheerio双杂合子，而它是正常的dFmr 1或cheerio的单杂合子。在dFmr 1突变体中，细丝蛋白（Cheerio）水平在间隔训练后低于正常水平。这些观察结果支持这样的观点，即减少肌动蛋白交联可能是脆性X患者和动物模型中长而细的树突棘持续存在的基础。更一般地说，我们的研究结果代表了在记忆形成的体内模型系统中精神发育迟滞基因之间的遗传相互作用的第一个证明。
The last decade has witnessed the identification of single-gene defects associated with an impressive number of mental retardation syndromes. Fragile X syndrome, the most common cause of mental retardation for instance, results from disruption of the FMR1 gene. Similarly, Periventricular Nodular Heterotopia, which includes cerebral malformation, epilepsy and cognitive disabilities, derives from disruption of the Filamin A gene. While it remains unclear whether defects in common molecular pathways may underlie the cognitive dysfunction of these various syndromes, defects in cytoskeletal structure nonetheless appear to be common to several mental retardation syndromes. FMR1 is known to interact with Rac, profilin, PAK and Ras, which are associated with dendritic spine defects. In Drosophila, disruptions of the dFmr1 gene impair long-term memory (LTM), and the Filamin A homolog (cheerio) was identified in a behavioral screen for LTM mutants. Thus, we investigated the possible interaction between cheerio and dFmr1 during LTM formation in Drosophila. We show that LTM specifically is defective in dFmr1/cheerio double heterozygotes, while it is normal in single heterozygotes for either dFmr1 or cheerio. In dFmr1 mutants, Filamin (Cheerio) levels are lower than normal after spaced training. These observations support the notion that decreased actin cross-linking may underlie the persistence of long and thin dendritic spines in Fragile X patients and animal models. More generally, our results represent the first demonstration of a genetic interaction between mental retardation genes in an in vivo model system of memory formation.
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影响因子：
3.7
作者：
Esue O;Tseng Y;Wirtz D
通讯作者：
Wirtz D
影响因子：
5.6
作者：
Battaglia, G;Granata, T;Avanzini, G
通讯作者：
Avanzini, G
DOI：
10.1002/ajmg.1320450120
发表时间：
1993-01-01
期刊：
AMERICAN JOURNAL OF MEDICAL GENETICS
影响因子：
--
作者：
BERRYKRAVIS, E;SKLENA, P
通讯作者：
SKLENA, P
影响因子：
3.5
作者：
Collins, AL;Levenson, JM;Zoghbi, HY
通讯作者：
Zoghbi, HY
影响因子：
64.8
作者：
Engert, F;Bonhoeffer, T
通讯作者：
Bonhoeffer, T