Afadin, a Ras/Rap effector that controls cadherin function, promotes spine and excitatory synapse density in the hippocampus.
Afadin, a Ras/Rap effector that controls cadherin function, promotes spine and excitatory synapse density in the hippocampus.
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DOI：
10.1523/jneurosci.4565-11.2012
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发表时间：
2012-01-04
期刊：
影响因子：
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通讯作者：
Reichardt LF
中科院分区：
文献类型：
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作者：
Beaudoin GM 3rd;Schofield CM;Nuwal T;Zang K;Ullian EM;Huang B;Reichardt LF
许多分子调节突触发生，但对其功能所需的细胞内信号传导途径知之甚少。Afadin是一种RAP调节的肌动蛋白结合蛋白，促进钙粘蛋白复合物组装以及结合许多其他细胞粘附分子和受体。为了研究其在介导突触发生中的作用，我们在有丝分裂后的海马神经元中使用条件等位基因删除afadin（mllt 1）。与其促进钙粘蛋白募集的作用一致，afadin缺失导致N-钙粘蛋白斑点减少70%且强度降低，β-连环蛋白和α N-连环蛋白斑点密度降低相似，EphB 2斑点密度降低35%。它的缺失还导致CA 1辐射层中的棘和兴奋性突触密度降低40%，这是通过形态学、突触前和突触后标记物的沉积以及突触传递来确定的。其余的突触似乎功能正常。因此，afadin是钙粘蛋白募集的关键细胞内信号分子，并且是体内棘和突触形成所必需的。
Many molecules regulate synaptogenesis, but intracellular signaling pathways required for their functions are poorly understood. Afadin is a Rap-regulated, actin-binding protein that promotes cadherin complex assembly as well as binding many other cell adhesion molecules and receptors. To examine its role in mediating synaptogenesis, we deleted afadin (mllt1), using a conditional allele, in post-mitotic hippocampal neurons. Consistent with its role in promoting cadherin recruitment, afadin deletion resulted in 70% fewer and less intense N-cadherin puncta with similar reductions of β-catenin and αN-catenin puncta densities, and 35% reduction in EphB2 puncta density. Its absence also resulted in 40% decreases in spine and excitatory synapse densities in the stratum radiatum of CA1, as determined by morphology, apposition of pre- and postsynaptic markers, and synaptic transmission. The remaining synapses appeared to function normally. Thus, afadin is a key intracellular signaling molecule for cadherin recruitment and is necessary for spine and synapse formation in vivo.