Neuroligin 1 is dynamically exchanged at postsynaptic sites.
Neuroligin 1 is dynamically exchanged at postsynaptic sites.
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DOI：
10.1523/jneurosci.0896-10.2010
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发表时间：
2010-09-22
期刊：
影响因子：
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通讯作者：
Kneussel M
中科院分区：
文献类型：
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作者：
Schapitz IU;Behrend B;Pechmann Y;Lappe-Siefke C;Kneussel SJ;Wallace KE;Stempel AV;Buck F;Grant SG;Schweizer M;Schmitz D;Schwarz JR;Holzbaur EL;Kneussel M
神经连接蛋白是突触后细胞黏附分子，与突触前神经尿毒素相关。这两个因子形成跨突触连接，在突触之间传递信号，指定突触功能，并在突触形成中发挥作用。神经连接蛋白功能障碍会损害突触传递，扰乱神经元网络，并被认为参与了认知疾病。在这里，我们报告了旨在诱导LTP或LTD的化学处理诱导神经连接蛋白1/3的转换，导致表膜蛋白水平的增加或降低。尽管GFP-Non-Ligin 1在跨突触的关键位置发挥结构作用，但随着时间的推移，它会通过LTD化学诱导的神经Ligin内化在海马神经元中留下突触，这依赖于完整的微管细胞骨架。因此，神经连接素1和它的结合伙伴PSD-95与动力蛋白运动复合体的成分结合，并与动力蛋白亚单位进行逆行共运输。转基因耗尽小鼠的动力蛋白功能会导致突触后NLG1/3和PSD-95的增加。同时，突触后密度(PSD)长度和脊柱头部大小显著增加，这与转基因过表达NLG1观察到的表型相似。此外，应用竞争性PSD-95多肽或神经连接素1C端突变，可特异性地改变神经连接素1表面膜的表达并干扰其内化。我们的数据表明，突触的可塑性通过主动的细胞骨架运输来调节神经连接素的周转。
Neuroligins are postsynaptic cell adhesion molecules that associate with presynaptic neurexins. Both factors form a transsynaptic connection, mediate signalling across the synapse, specify synaptic functions and play a role in synapse formation. Neuroligin dysfunction impairs synaptic transmission, disrupts neuronal networks and is thought to participate in cognitive diseases. Here we report that chemical treatment designed to induce LTP or LTD induces neuroligin 1/3 turnover, leading to either increased or decreased surface membrane protein levels, respectively. Despite its structural role at a crucial transsynaptic position, GFP-neuroligin 1 leaves synapses in hippocampal neurons over time with chemical LTD-induced neuroligin internalization depending on an intact microtubule cytoskeleton. Accordingly, neuroligin 1 and its binding partner PSD-95 associate with components of the dynein motor complex and undergo retrograde co-transport with a dynein-subunit. Transgenic depletion of dynein function in mice causes postsynaptic NLG1/3 and PSD-95 enrichment. In parallel, postsynaptic density (PSD) lengths and spine head sizes are significantly increased, a similar phenotype as observed upon transgenic overexpression of NLG1. Moreover, application of a competitive PSD-95 peptide or neuroligin 1 C-terminal mutagenesis, specifically alter neuroligin 1 surface membrane expression and interfere with its internalization. Our data suggest the concept that synaptic plasticity regulates neuroligin turnover through active cytoskeleton transport.