Drebrin A regulates dendritic spine plasticity and synaptic function in mature cultured hippocampal neurons
Drebrin A regulates dendritic spine plasticity and synaptic function in mature cultured hippocampal neurons
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DOI：
10.1242/jcs.033464
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发表时间：
2009-02-15
影响因子：
4
通讯作者：
Ferhat, Lotfi
中科院分区：
文献类型：
--
作者：
Ivanov, Anton;Esclapez, Monique;Ferhat, Lotfi
树突A是最丰富的神经元特异性F-肌动蛋白结合蛋白之一，仅在树突中发现，特别集中在接受兴奋性输入的树突棘中。我们研究了dreplastin A在突触传递中的作用，发现dreplastin A的过表达增强了突触能突触传递，可能是通过增加活性突触部位密度。有趣的是，尽管GABA能突触密度和传递效率没有改变，但drexA的过表达也影响了微型抑制性突触后电流（mIPSC）的频率、振幅和动力学。下调dreplastin A导致谷氨酸能和GABA能突触活动的减少。在异源细胞中，dreplastin A重组和稳定F-肌动蛋白，这些作用是由其肌动蛋白结合结构域介导的。因此，dreplasma A可能通过调节肌动蛋白细胞骨架的重塑和动力学来调节树突棘的形态。我们的数据首次表明，dreamatA调节谷氨酸能和GABA能突触活动。
Drebrin A, one of the most abundant neuron-specific F-actinbinding proteins, is found exclusively in dendrites and is particularly concentrated in dendritic spines receiving excitatory inputs. We investigated the role of drebrin A in synaptic transmission and found that overexpression of drebrin A augmented the glutamatergic synaptic transmission, probably through an increase of active synaptic site density. Interestingly, overexpression of drebrin A also affected the frequency, amplitude and kinetics of miniature inhibitory postsynaptic currents (mIPSCs), despite the fact that GABAergic synapse density and transmission efficacy were not modified. Downregulation of drebrin A led to a decrease of both glutamatergic and GABAergic synaptic activity. In heterologous cells, drebrin A reorganized and stabilized F-actin and these effects were mediated by its actin-binding domain. Thus, drebrin A might regulate dendritic spine morphology via regulation of actin cytoskeleton remodeling and dynamics. Our data demonstrate for the first time that drebrin A modulates glutamatergic and GABAergic synaptic activities.