Konno Daijiro, Ko Ji-Ae, Usui Shinichi, Hori Kei, Maruoka Hisato, Inui Makoto, Fujikado Takashi, Tano Yasuo, Suzuki Tatsuo, Tohyama Koujiro, Sobue Kenji
Department of Neuroscience (D13), 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
J Cell Sci. 2002 Dec 1;115(Pt 23):4695-706. doi: 10.1242/jcs.00127.
The postsynaptic site of the excitatory synapse, which is composed of the postsynaptic density (PSD) attached to the postsynaptic membrane, is a center for synaptic plasticity. To reveal the molecular organization and functional regulation of the postsynaptic site, we cloned a 70 kDa protein that is concentrated in PSDs using a monoclonal antibody against the PSD. This protein, named PSD-Zip70, is highly homologous to the human FEZ1/LZTS1 gene product. PSD-Zip70 contains an N-myristoylation consensus sequence, a polybasic cluster in the N-terminal region and four leucine-zipper motifs in the C-terminal region. Light and electron microscopy showed that this protein was localized to the dendritic spines, especially in the PSD and the postsynaptic membrane. Fractionation of the synaptic plasma membrane demonstrated that PSD-Zip70 was localized to the PSD and the dendritic raft. In Madin-Darby canine kidney (MDCK) cells, exogenous PSD-Zip70 was targeted to the apical plasma membrane of microvilli, and its N-myristoylation was necessary for this targeting. In hippocampal neurons, N-myristoylation was also required for the membrane localization and the C-terminal region was critically involved in the synaptic targeting. These results suggest that PSD-Zip70 may be involved in the dynamic properties of the structure and function of the postsynaptic site.
兴奋性突触的突触后位点由附着于突触后膜的突触后致密区（PSD）组成，是突触可塑性的中心。为了揭示突触后位点的分子组织和功能调节，我们使用针对PSD的单克隆抗体克隆了一种集中在PSD中的70 kDa蛋白质。这种名为PSD-Zip70的蛋白质与人类FEZ1/LZTS1基因产物高度同源。PSD-Zip70包含一个N-肉豆蔻酰化共有序列、N端区域的一个多碱性簇和C端区域的四个亮氨酸拉链基序。光学显微镜和电子显微镜显示，这种蛋白质定位于树突棘，尤其是在PSD和突触后膜中。突触质膜的分级分离表明，PSD-Zip70定位于PSD和树突筏。在Madin-Darby犬肾（MDCK）细胞中，外源性PSD-Zip70靶向微绒毛的顶端质膜，其N-肉豆蔻酰化对于这种靶向是必需的。在海马神经元中，N-肉豆蔻酰化对于膜定位也是必需 的，并且C端区域在突触靶向中起关键作用。这些结果表明，PSD-Zip70可能参与突触后位点结构和功能的动态特性。
