Boeckers T M
Department of Anatomy and Cell Biology, Ulm University, 89081 Ulm, Germany.
Cell Tissue Res. 2006 Nov;326(2):409-22. doi: 10.1007/s00441-006-0274-5. Epub 2006 Jul 25.
Glutamatergic synapses in the central nervous system are characterized by an electron-dense web underneath the postsynaptic membrane; this web is called the postsynaptic density (PSD). PSDs are composed of a dense network of several hundred proteins, creating a macromolecular complex that serves a wide range of functions. Prominent PSD proteins such as members of the MaGuk or ProSAP/Shank family build up a dense scaffold that creates an interface between clustered membrane-bound receptors, cell adhesion molecules and the actin-based cytoskeleton. Moreover, kinases, phosphatases and several proteins of different signalling pathways are specifically localized within the spine/PSD compartment. Small GTPases and regulating proteins are also enriched in PSDs being the molecular basis for regulated structural changes of cytoskeletal components within the synapse in response to external or internal stimuli, e.g. synaptic activation. This synaptic rearrangement (structural plasticity) is a rapid process and is believed to underlie learning and memory formation. The characterization of synapse/PSD proteins is especially important in the light of recent data suggesting that several mental disorders have their molecular defect at the synapse/PSD level.
中枢神经系统中的谷氨酸能突触的特征是在突触后膜下方有一个电子致密网络;这个网络被称为突触后致密物(PSD)。PSD由数百种蛋白质组成的密集网络构成,形成一个具有广泛功能的大分子复合物。突出的PSD蛋白,如MaGuk或ProSAP/Shank家族的成员,构建了一个密集的支架,在聚集的膜结合受体、细胞粘附分子和基于肌动蛋白的细胞骨架之间形成一个界面。此外,激酶、磷酸酶和不同信号通路的几种蛋白质特异性地定位于棘突/PSD区室。小GTP酶和调节蛋白也在PSD中富集,它们是突触内细胞骨架成分响应外部或内部刺激(如突触激活)而发生结构变化的分子基础。这种突触重排(结构可塑性)是一个快速过程,被认为是学习和记忆形成的基础。鉴于最近的数据表明几种精神障碍在突触/PSD水平存在分子缺陷,对突触/PSD蛋白的表征尤为重要。