The female epilepsy protein PCDH19 is a new GABAAR-binding partner that regulates GABAergic transmission as well as migration and morphological maturation of hippocampal neurons.
The female epilepsy protein PCDH19 is a new GABAAR-binding partner that regulates GABAergic transmission as well as migration and morphological maturation of hippocampal neurons.
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DOI：
10.1093/hmg/ddy019
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发表时间：
2018-03-15
影响因子：
3.5
通讯作者：
Passafaro M
中科院分区：
文献类型：
--
作者：
Bassani S;Cwetsch AW;Gerosa L;Serratto GM;Folci A;Hall IF;Mazzanti M;Cancedda L;Passafaro M
PCDH 19基因（Xp22.1）编码细胞粘附蛋白原钙粘蛋白-19（PCDH 19），并且负责以女性局限性癫痫、认知障碍和自闭症特征为特征的神经发育病理学，其致病机制仍有待阐明。在这里，我们确定了一个新的相互作用PCDH 19和GABAA受体（GABAAR）α亚基在大鼠大脑。PCDH 19 shRNA介导的下调减少GABAAR表面表达，并影响培养的海马神经元中微型抑制性突触后电流（mIPSC）的频率和动力学。在体内，PCDH 19下调损害CA 1海马神经元的迁移，定向和树突状分支，并增加大鼠癫痫发作的易感性。总之，这些数据表明PCDH 19在GABA能传递以及神经元的迁移和形态成熟中的作用。
The PCDH19 gene (Xp22.1) encodes the cell-adhesion protein protocadherin-19 (PCDH19) and is responsible for a neurodevelopmental pathology characterized by female-limited epilepsy, cognitive impairment and autistic features, the pathogenic mechanisms of which remain to be elucidated. Here, we identified a new interaction between PCDH19 and GABAA receptor (GABAAR) alpha subunits in the rat brain. PCDH19 shRNA-mediated downregulation reduces GABAAR surface expression and affects the frequency and kinetics of miniature inhibitory postsynaptic currents (mIPSCs) in cultured hippocampal neurons. In vivo, PCDH19 downregulation impairs migration, orientation and dendritic arborization of CA1 hippocampal neurons and increases rat seizure susceptibility. In sum, these data indicate a role for PCDH19 in GABAergic transmission as well as migration and morphological maturation of neurons.
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DOI：
10.1083/jcb.201507108
发表时间：
2015-11-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Cooper SR;Emond MR;Duy PQ;Liebau BG;Wolman MA;Jontes JD
通讯作者：
Jontes JD
DOI：
10.1083/jcb.201007008
发表时间：
2010-11-29
期刊：
The Journal of cell biology
影响因子：
--
作者：
Biswas S;Emond MR;Jontes JD
通讯作者：
Jontes JD
影响因子：
2.5
作者：
Cohen, AS;Lin, DD;Coulter, DA
通讯作者：
Coulter, DA
影响因子：
2.7
作者：
Emond, Michelle R.;Biswas, Sayantanee;Jontes, James D.
通讯作者：
Jontes, James D.
影响因子：
3.4
作者：
Hutcheon, B;Fritschy, JM;Poulter, MO
通讯作者：
Poulter, MO