Missler Markus, Zhang Weiqi, Rohlmann Astrid, Kattenstroth Gunnar, Hammer Robert E, Gottmann Kurt, Südhof Thomas C
Center for Basic Neuroscience, Department of Molecular Genetics, Dallas, Texas 75390-9111, USA.
Nature. 2003 Jun 26;423(6943):939-48. doi: 10.1038/nature01755.
Synapses are specialized intercellular junctions in which cell adhesion molecules connect the presynaptic machinery for neurotransmitter release to the postsynaptic machinery for receptor signalling. Neurotransmitter release requires the presynaptic co-assembly of Ca2+ channels with the secretory apparatus, but little is known about how synaptic components are organized. Alpha-neurexins, a family of >1,000 presynaptic cell-surface proteins encoded by three genes, link the pre- and postsynaptic compartments of synapses by binding extracellularly to postsynaptic cell adhesion molecules and intracellularly to presynaptic PDZ domain proteins. Using triple-knockout mice, we show that alpha-neurexins are not required for synapse formation, but are essential for Ca2+-triggered neurotransmitter release. Neurotransmitter release is impaired because synaptic Ca2+ channel function is markedly reduced, although the number of cell-surface Ca2+ channels appears normal. These data suggest that alpha-neurexins organize presynaptic terminals by functionally coupling Ca2+ channels to the presynaptic machinery.
突触是一种特殊的细胞间连接，其中细胞粘附分子将用于神经递质释放的突触前机制与用于受体信号传导的突触后机制连接起来。神经递质的释放需要钙离子通道与分泌装置在突触前共同组装，但对于突触成分如何组织却知之甚少。α-神经连蛋白是一个由三个基因编码的超过1000种突触前细胞表面蛋白的家族，它通过细胞外与突触后细胞粘附分子结合以及细胞内与突触前PDZ结构域蛋白结合，将突触的突触前和突触后部分连接起来。利用三基因敲除小鼠，我们发现α-神经连蛋白对于突触形成不是必需的，但对于钙离子触发的神经递质释放至关重要。尽管细胞表面钙离子通道的数量看起来正常，但神经递质释放受损是因为突触钙离子通道功能明显降低。这些数据表明，α-神经连蛋白通过将钙离子通道与突触前机制功能偶联来组织突触前终末。
