PRICKLE1 interaction with SYNAPSIN I reveals a role in autism spectrum disorders.
PRICKLE1 interaction with SYNAPSIN I reveals a role in autism spectrum disorders.
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DOI：
10.1371/journal.pone.0080737
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Bassuk AG
中科院分区：
文献类型：
--
作者：
Paemka L;Mahajan VB;Skeie JM;Sowers LP;Ehaideb SN;Gonzalez-Alegre P;Sasaoka T;Tao H;Miyagi A;Ueno N;Takao K;Miyakawa T;Wu S;Darbro BW;Ferguson PJ;Pieper AA;Britt JK;Wemmie JA;Rudd DS;Wassink T;El-Shanti H;Mefford HC;Carvill GL;Manak JR;Bassuk AG
自闭症谱系障碍（ASDs）与癫痫的常见合并症表明它们具有共同的潜在遗传易感性；一些基因一旦发生突变，就会导致这两种疾病。最近，发现了与ASD分离的PRICKLE1错义突变。然而，该基因突变可能导致ASD的机制尚不清楚。为了阐明皮刺1在自闭症中的作用，我们在皮刺1+/−小鼠、果蝇、酵母和神经细胞系中进行了研究。我们发现携带Prickle1突变的小鼠表现出asd样行为。为了寻找在中枢神经系统中与PRICKLE1相互作用的蛋白，我们利用人脑cDNA文库进行酵母双杂交筛选，并分离出与SYNAPSIN I （SYN1）同源的肽，SYN1是一种参与突触发生、突触囊泡形成和神经递质释放调节的蛋白。内源性Prickle1和Syn1在神经元中共定位，并通过在ASD和癫痫中突变的Syn1区域进行物理相互作用。最后，在PC12细胞中，一个突变的PRICKLE1破坏了其增加致密核囊泡大小的能力。综上所述，这些发现表明，PRICKLE1突变通过破坏与SYN1的相互作用和突触囊泡的调节而导致ASD。
The frequent comorbidity of Autism Spectrum Disorders (ASDs) with epilepsy suggests a shared underlying genetic susceptibility; several genes, when mutated, can contribute to both disorders. Recently, PRICKLE1 missense mutations were found to segregate with ASD. However, the mechanism by which mutations in this gene might contribute to ASD is unknown. To elucidate the role of PRICKLE1 in ASDs, we carried out studies in Prickle1+/− mice and Drosophila, yeast, and neuronal cell lines. We show that mice with Prickle1 mutations exhibit ASD-like behaviors. To find proteins that interact with PRICKLE1 in the central nervous system, we performed a yeast two-hybrid screen with a human brain cDNA library and isolated a peptide with homology to SYNAPSIN I (SYN1), a protein involved in synaptogenesis, synaptic vesicle formation, and regulation of neurotransmitter release. Endogenous Prickle1 and Syn1 co-localize in neurons and physically interact via the SYN1 region mutated in ASD and epilepsy. Finally, a mutation in PRICKLE1 disrupts its ability to increase the size of dense-core vesicles in PC12 cells. Taken together, these findings suggest PRICKLE1 mutations contribute to ASD by disrupting the interaction with SYN1 and regulation of synaptic vesicles.
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DOI：
10.1073/pnas.1112667108
发表时间：
2011-09-13
影响因子：
11.1
作者：
Bader, Patrick L.;Faizi, Mehrdad;Shamloo, Mehrdad
通讯作者：
Shamloo, Mehrdad
影响因子：
2.2
作者：
Etholm, Lars;Bahonjic, Elma;Heggelund, Paul
通讯作者：
Heggelund, Paul
DOI：
10.1176/appi.ajp.2010.10040484
发表时间：
2010-12
期刊：
The American journal of psychiatry
影响因子：
--
作者：
Feyder M;Karlsson RM;Mathur P;Lyman M;Bock R;Momenan R;Munasinghe J;Scattoni ML;Ihne J;Camp M;Graybeal C;Strathdee D;Begg A;Alvarez VA;Kirsch P;Rietschel M;Cichon S;Walter H;Meyer-Lindenberg A;Grant SG;Holmes A
通讯作者：
Holmes A
影响因子：
3.8
作者：
GRAHAM, FL;SMILEY, J;NAIRN, R
通讯作者：
NAIRN, R
影响因子：
9.8
作者：
Arking, Dan E.;Cutler, David J.;Chakravarti, Aravinda
通讯作者：
Chakravarti, Aravinda