Afadin regulates puncta adherentia junction formation and presynaptic differentiation in hippocampal neurons.
Afadin regulates puncta adherentia junction formation and presynaptic differentiation in hippocampal neurons.
复制标题
DOI：
10.1371/journal.pone.0089763
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Takai Y
中科院分区：
文献类型：
--
作者：
Toyoshima D;Mandai K;Maruo T;Supriyanto I;Togashi H;Inoue T;Mori M;Takai Y
海马透明层苔藓纤维-CA 3锥体细胞突触的形成和重塑与学习记忆的细胞基础有关。Afadin及其结合细胞粘附分子nectin-1和nectin-3与N-钙粘蛋白一起集中在这些突触中的粘附点连接（PAJ）处。在这里，我们研究了afadin在苔藓纤维-CA 3锥体细胞突触的PAJ形成和突触前分化中的作用。在这些突触的小鼠，其中afadin基因有条件地失活突触前使用nestin-Cre小鼠，免疫荧光信号的PAJ组件，nectin-1，nectin-3和N-cadherin，几乎完全消失，而突触前组件，VGLUT 1和巴松管，显着减少。此外，这些信号在培养的afadin缺陷海马神经元中显著降低。此外，与对照组相比，afadin缺陷组海马神经元的微小兴奋性突触后电流的间隔时间延长，表明afadin缺陷组神经元突触前功能受到抑制或突触数量减少。突触前囊泡回收和配对记录的分析表明，培养的afadin缺陷的神经元表现出受损的突触前功能。这些结果表明，afadin调节PAJ的形成和突触前分化在大多数苔藓纤维CA 3锥体细胞突触，而在相当数量的这些神经元，afadin调节PAJ的形成，但不突触前分化。
The formation and remodeling of mossy fiber-CA3 pyramidal cell synapses in the stratum lucidum of the hippocampus are implicated in the cellular basis of learning and memory. Afadin and its binding cell adhesion molecules, nectin-1 and nectin-3, together with N-cadherin, are concentrated at puncta adherentia junctions (PAJs) in these synapses. Here, we investigated the roles of afadin in PAJ formation and presynaptic differentiation in mossy fiber-CA3 pyramidal cell synapses. At these synapses in the mice in which the afadin gene was conditionally inactivated before synaptogenesis by using nestin-Cre mice, the immunofluorescence signals for the PAJ components, nectin-1, nectin-3 and N-cadherin, disappeared almost completely, while those for the presynaptic components, VGLUT1 and bassoon, were markedly decreased. In addition, these signals were significantly decreased in cultured afadin-deficient hippocampal neurons. Furthermore, the interevent interval of miniature excitatory postsynaptic currents was prolonged in the cultured afadin-deficient hippocampal neurons compared with control neurons, indicating that presynaptic functions were suppressed or a number of synapse was reduced in the afadin-deficient neurons. Analyses of presynaptic vesicle recycling and paired recordings revealed that the cultured afadin-deficient neurons showed impaired presynaptic functions. These results indicate that afadin regulates both PAJ formation and presynaptic differentiation in most mossy fiber-CA3 pyramidal cell synapses, while in a considerable population of these neurons, afadin regulates only PAJ formation but not presynaptic differentiation.
登录
查看更多内容
影响因子：
16.2
作者：
Togashi, H;Abe, K;Takeichi, M
通讯作者：
Takeichi, M
Afadin：胚胎发生过程中极化上皮细胞-细胞连接结构组织所必需的关键分子。
DOI：
10.1083/jcb.146.5.1117
发表时间：
1999-09-06
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ikeda W;Nakanishi H;Miyoshi J;Mandai K;Ishizaki H;Tanaka M;Togawa A;Takahashi K;Nishioka H;Yoshida H;Mizoguchi A;Nishikawa S;Takai Y
通讯作者：
Takai Y
Afadin：一种新型的肌动蛋白结合蛋白，其中一个PDZ结构域位于基于钙粘蛋白的细胞到细胞粘附连接处。
影响因子：
7.8
作者：
Mandai, K;Nakanishi, H;Satoh, A;Obaishi, H;Wada, M;Nishioka, H;Itoh, M;Mizoguchi, A;Aoki, T;Fujimoto, T;Matsuda, Y;Tsukita, S;Takai, Y
通讯作者：
Takai, Y
巴松管是一种新型的锌指CAG/谷氨酰胺重复蛋白，选择性地定位于突触前神经末端的活性区域。
影响因子：
7.8
作者：
Dieck, ST;Sanmartí-Vila, L;Langnaese, K;Richter, K;Kindler, S;Soyke, A;Wex, H;Smalla, KH;Kämpf, U;Fränzer, JT;Stumm, M;Garner, CC;Gundelfinger, ED
通讯作者：
Gundelfinger, ED
影响因子：
56.9
作者：
Bellocchio, EE;Reimer, RJ;Edwards, RH
通讯作者：
Edwards, RH