Takeuchi Tomonori, Miyazaki Taisuke, Watanabe Masahiko, Mori Hisashi, Sakimura Kenji, Mishina Masayoshi
Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo, and Solution Oriented Research for Science and Technology, Japan Science and Technology Agency, Tokyo 113-0033, Japan.
J Neurosci. 2005 Feb 23;25(8):2146-56. doi: 10.1523/JNEUROSCI.4740-04.2005.
Precise topological matching of presynaptic and postsynaptic specializations is essential for efficient synaptic transmission. Furthermore, synaptic connections are subjected to rearrangements throughout life. Here we examined the role of glutamate receptor (GluR) delta2 in the adult brain by inducible and cerebellar Purkinje cell (PC)-specific gene targeting under the pure C57BL/6 genetic background. Concomitant with the decrease of postsynaptic GluRdelta2 proteins, presynaptic active zones shrank progressively and postsynaptic density (PSD) expanded, resulting in mismatching between presynaptic and postsynaptic specializations at parallel fiber-PC synapses. Furthermore, GluRdelta2 and PSD-93 proteins were concentrated at the contacted portion of mismatched synapses, whereas AMPA receptors were distributed in both the contacted and dissociated portions. When GluRdelta2 proteins were diminished, PC spines lost their synaptic contacts. We thus identified postsynaptic GluRdelta2 as a key regulator of the presynaptic active zone and PSD organization at parallel fiber-PC synapses in the adult brain.
突触前和突触后特化结构的精确拓扑匹配对于高效的突触传递至关重要。此外，突触连接在整个生命过程中都会发生重排。在这里，我们通过在纯C57BL/6遗传背景下进行诱导性和小脑浦肯野细胞（PC）特异性基因靶向，研究了谷氨酸受体（GluR）δ2在成体大脑中的作用。随着突触后GluRδ2蛋白的减少，突触前活性区逐渐缩小，突触后致密区（PSD）扩大，导致平行纤维-PC突触的突触前和突触后特化结构不匹配。此外，GluRδ2和PSD-93蛋白集中在不匹配突触的接触部分，而AMPA受体则分布在接触部分和解离部分。当GluRδ2蛋白减少时，PC树突棘失去突触联系。因此，我们确定突触后GluRδ2是成体大脑中平行纤维-PC突触的突触前活性区和PSD组织的关键调节因子。
