Dact1 is a postsynaptic protein required for dendrite, spine, and excitatory synapse development in the mouse forebrain.
Dact1 is a postsynaptic protein required for dendrite, spine, and excitatory synapse development in the mouse forebrain.
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DOI：
10.1523/jneurosci.0354-10.2010
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发表时间：
2010-03-24
期刊：
影响因子：
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通讯作者：
Cheyette BN
中科院分区：
文献类型：
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作者：
Okerlund ND;Kivimäe S;Tong CK;Peng IF;Ullian EM;Cheyette BN
Dact 1（Dapper/Frodo）是一种细胞内磷蛋白，与Dishevelled、连环蛋白和其他信号蛋白结合，在发育和成熟的哺乳动物中枢神经系统中表达，但其功能尚不清楚。Dact 1与突触标记共定位，并从培养的小鼠前脑神经元中分配到突触后组分。与野生型同窝小鼠相比，Dact 1基因敲除小鼠的海马神经元具有更简单的树枝状树枝和更少的棘。这与兴奋性突触和微型兴奋性突触后电流的减少有关，而抑制性突触不受影响。Dact 1的缺失导致激活的Rac减少，Dact 1或组成型活性Rac的重组表达，但不是Rho或Cdc 42，挽救了Dact 1突变神经元中的树突和棘表型。我们的研究结果表明，在神经元分化Dact 1起着至关重要的作用，在分子途径促进Rac活性的基础上的树突的加工和建立的棘和兴奋性突触。
Dact1 (Dapper/Frodo), an intracellular phosphoprotein that binds Dishevelled, catenins, and other signaling proteins, is expressed in the developing and mature mammalian central nervous system, but its function there is unknown. Dact1 colocalized with synaptic markers and partitioned to postsynaptic fractions from cultured mouse forebrain neurons. Hippocampal neurons from Dact1 knockout mice had simpler dendritic arbors and fewer spines than hippocampal neurons from wild type littermates. This correlated with reductions in excitatory synapses and miniature excitatory postsynaptic currents, whereas inhibitory synapses were not affected. Loss of Dact1 resulted in a decrease in activated Rac, and recombinant expression of either Dact1 or constitutively active Rac, but not Rho or Cdc42, rescued dendrite and spine phenotypes in Dact1 mutant neurons. Our findings suggest that during neuronal differentiation Dact1 plays a critical role in a molecular pathway promoting Rac activity underlying the elaboration of dendrites and the establishment of spines and excitatory synapses.