Dresbach Thomas, Neeb Antje, Meyer Guido, Gundelfinger Eckart D, Brose Nils
Institute for Anatomy and Cell Biology, Ruprecht-Karls-University Heidelberg, D-69120 Heidelberg, Germany.
Mol Cell Neurosci. 2004 Nov;27(3):227-35. doi: 10.1016/j.mcn.2004.06.013.
Synaptic cell adhesion and synaptogenesis are thought to involve the interaction of neuroligin, a postsynaptic transmembrane protein, with its presynaptic ligand neurexin. Neuroligin also interacts with SAP90/PSD95, a multidomain scaffolding protein thought to recruit proteins to postsynaptic sites. Using expression of GFP-tagged versions of neuroligin in cultured hippocampal neurons, we find that neuroligin is targeted to synapses via intracellular sequences distinct from its SAP90/PSD95 binding site. A neuroligin mutant lacking the intracellular domain fails to target to synapses. These data indicate that postsynaptic targeting of neuroligin does not rely on the scaffolding action of SAP90/PSD95 and is not induced by binding to presynaptic neurexin. Neuroligin is rather targeted to synapses via a postsynaptic mechanism, which may precede and be necessary for subsequent recruitment of neurexin and other neuroligin interactors such as SAP90/PSD95, suggesting a pivotal position for neuroligin in a putative hierarchy of interactions assembling or stabilizing synapses.
突触细胞黏附和突触形成被认为涉及神经配蛋白（一种突触后跨膜蛋白）与其突触前配体神经连接蛋白的相互作用。神经配蛋白还与SAP90/PSD95相互作用，SAP90/PSD95是一种多结构域支架蛋白，被认为可将蛋白质招募到突触后位点。通过在培养的海马神经元中表达绿色荧光蛋白标记的神经配蛋白版本，我们发现神经配蛋白通过与其SAP90/PSD95结合位点不同的细胞内序列靶向突触。缺乏细胞内结构域的神经配蛋白突变体无法靶向突触。这些数据表明，神经配蛋白的突触后靶向不依赖于SAP90/PSD95的支架作用，也不是由与突触前神经连接蛋白的结合所诱导的。相反，神经配蛋白是通过一种突触后机制靶向突触的，这种机制可能先于并为随后招募神经连接蛋白和其他神经配蛋白相互作用分子（如SAP90/PSD95）所必需，这表明神经配蛋白在组装或稳定突触的假定相互作用层级中处于关键位置。
