Dean Camin, Scholl Francisco G, Choih Jenny, DeMaria Shannon, Berger James, Isacoff Ehud, Scheiffele Peter
Department of Molecular and Cell Biology, University of California, Berkeley, 271 LSA, California 94720, USA.
Nat Neurosci. 2003 Jul;6(7):708-16. doi: 10.1038/nn1074.
Neurexins are a large family of proteins that act as neuronal cell-surface receptors. The function and localization of the various neurexins, however, have not yet been clarified. Beta-neurexins are candidate receptors for neuroligin-1, a postsynaptic membrane protein that can trigger synapse formation at axon contacts. Here we report that neurexins are concentrated at synapses and that purified neuroligin is sufficient to cluster neurexin and to induce presynaptic differentiation. Oligomerization of neuroligin is required for its function, and we find that beta-neurexin clustering is sufficient to trigger the recruitment of synaptic vesicles through interactions that require the cytoplasmic domain of neurexin. We propose a two-step model in which postsynaptic neuroligin multimers initially cluster axonal neurexins. In response to this clustering, neurexins nucleate the assembly of a cytoplasmic scaffold to which the exocytotic apparatus is recruited.
神经连接蛋白是一类作为神经元细胞表面受体的蛋白质大家族。然而，各种神经连接蛋白的功能和定位尚未明确。β-神经连接蛋白是神经配蛋白-1的候选受体，神经配蛋白-1是一种突触后膜蛋白，可在轴突接触处触发突触形成。在此我们报告，神经连接蛋白集中在突触处，并且纯化的神经配蛋白足以使神经连接蛋白聚集并诱导突触前分化。神经配蛋白的寡聚化是其功能所必需的，并且我们发现β-神经连接蛋白的聚集足以通过需要神经连接蛋白胞质结构域的相互作用来触发突触小泡的募集。我们提出了一个两步模型，其中突触后神经配蛋白多聚体首先聚集轴突神经连接蛋白。作为对这种聚集的响应，神经连接蛋白促使胞质支架组装，胞吐装置被募集到该支架上。
