Neurexins physically and functionally interact with GABA(A) receptors.
Neurexins physically and functionally interact with GABA(A) receptors.
复制标题
DOI：
10.1016/j.neuron.2010.04.008
复制
发表时间：
2010-05-13
期刊：
影响因子：
16.2
通讯作者：
Sudhof, Thomas C.
中科院分区：
文献类型：
--
作者：
Zhang, Chen;Atasoy, Deniz;Arac, Demet;Yang, Xiaofei;Fucillo, Marc V.;Robison, Alfred J.;Ko, Jaewon;Brunger, Axel T.;Sudhof, Thomas C.
神经素是突触前细胞粘附分子，与突触后神经素形成跨突触复合物。当在非神经元细胞中过度表达时，神经毒素诱导共培养神经元突触后特化的形成，这表明神经毒素是突触原性的。然而，我们现在发现，当神经毒素在神经元中过表达时，并不增加突触密度，而是选择性地抑制gabaergy突触的传递，而不减少gabaergy突触的数量。这种抑制是由所有测试的神经素亚型介导的，以细胞自主和神经素独立的方式。引人注目的是，在培养的神经元中以亚微摩尔浓度添加重组神经rexin诱导gaba能突触传递的抑制与神经rexin过表达相同。此外，用天然脑蛋白和纯化的重组蛋白进行的实验表明，神经毒素直接和化学计量地结合gabaa -受体，表明它们通过与gabaa -受体相互作用来降低gabaa能突触反应。我们的研究结果表明，除了其他文献记载的相互作用外，突触前神经毒素还直接作用于突触后gabaa受体，这可能有助于调节大脑的兴奋/抑制平衡。
Neurexins are presynaptic cell-adhesion molecules that form trans-synaptic complexes with postsynaptic neuroligins. When overexpressed in non-neuronal cells, neurexins induce formation of postsynaptic specializations in co-cultured neurons, suggesting that neurexins are synaptogenic. However, we now find that when overexpressed in neurons, neurexins do not increase synapse density, but instead selectively suppressed GABAergic synaptic transmission without decreasing GABAergic synapse numbers. This suppression was mediated by all subtypes of neurexins tested, in a cell-autonomous and neuroligin-independent manner. Strikingly, addition of recombinant neurexin to cultured neurons at sub-micromolar concentrations induced the same suppression of GABAergic synaptic transmission as neurexin overexpression. Moreover, experiments with native brain proteins and with purified recombinant proteins revealed that neurexins directly and stoichiometrically bind to GABAA-receptors, suggesting that they decrease GABAergic synaptic responses by interacting with GABAA-receptors. Our findings suggest that besides their other well-documented interactions, presynaptic neurexins directly act on postsynaptic GABAA-receptors, which may contribute to regulate the excitatory/inhibitory balance in brain.
登录
查看更多内容
影响因子：
16.2
作者：
Ko, Jaewon;Fuccillo, Marc V.;Malenka, Robert C.;Suedhof, Thomas C.
通讯作者：
Suedhof, Thomas C.
影响因子：
4.8
作者：
Gallagher, MJ;Shen, WZ;Macdonald, RL
通讯作者：
Macdonald, RL
影响因子：
3.5
作者：
Chih, B;Afridi, SK;Scheiffele, P
通讯作者：
Scheiffele, P
影响因子：
3.5
作者：
Lachman, Herbert M.;Fann, Cathy S. J.;Knowles, James A.
通讯作者：
Knowles, James A.
影响因子：
11.4
作者：
Ko, Jaewon;Zhang, Chen;Suedhof, Thomas C.
通讯作者：
Suedhof, Thomas C.