Kirsch J, Wolters I, Triller A, Betz H
Department of Neurochemistry, Max-Planck-Institute for Brain Research, Frankfurt/Main, Germany.
Nature. 1993;366(6457):745-8. doi: 10.1038/366745a0.
Each neuron in the mammalian brain carries many postsynaptic membrane specializations containing high densities of receptors that mediate signal transduction upon neurotransmitter release from the apposed nerve terminal. Little is known about the mechanisms by which receptors are transported to and anchored at postsynaptic sites, but extracellular as well as intracellular components may be involved. Ultrastructural studies have shown that the peripheral membrane protein gephyrin, which co-purifies with the postsynaptic inhibitory glycine receptor (GlyR) upon affinity chromatography, is situated on the cytoplasmic face of glycinergic postsynaptic membranes. Moreover, gephyrin binds with high affinity to polymerized tubulin and has been postulated to link the GlyR to the subsynaptic cytoskeleton. Here we report that treatment of rat spinal neurons in culture with gephyrin antisense oligonucleotides prevents the formation of GlyR clusters in the dendritic plasma membrane. Thus, gephyrin is essential for localizing the GlyR to presumptive postsynaptic plasma membrane specializations.
哺乳动物大脑中的每个神经元都带有许多突触后膜特化结构，这些结构含有高密度的受体，当神经递质从相对的神经末梢释放时，这些受体介导信号转导。关于受体被转运到突触后位点并锚定在该位点的机制，人们知之甚少，但细胞外以及细胞内成分可能都参与其中。超微结构研究表明，在亲和层析中与突触后抑制性甘氨酸受体（GlyR）共纯化的外周膜蛋白gephyrin，位于甘氨酸能突触后膜的胞质面上。此外，gephyrin与聚合微管蛋白具有高亲和力结合，并被推测可将GlyR与突触下细胞骨架相连。在此我们报告，用gephyrin反义寡核苷酸处理培养的大鼠脊髓神经元，可阻止树突质膜中GlyR簇的形成。因此，gephyrin对于将GlyR定位到假定的突触后质膜特化结构至关重要。
