期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：12
页码：4912-4916
DOI：10.1073/pnas.0900892106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Synaptic adhesion molecules such as neuroligin are involved in synapse formation, whereas ionotropic transmitter receptors mediate fast synaptic transmission. In mutant mice deficient in the glutamate receptor {delta}2 subunit ({delta}2), the number of synapses between granule neurons (GNs) and a Purkinje neuron (PN) in the cerebellum is reduced. Here, we have examined the role of {delta}2 in synapse formation using culture preparations. First, we found that the size and number of GN presynaptic terminals on a PN in the primary culture prepared from knockout mice were smaller than those in control culture. Next we expressed {delta}2 in nonneuronal human embryonic kidney (HEK) cells and cocultured them with GNs. Punctate structures expressing marker proteins for glutamatergic presynaptic terminals were accumulated around the HEK cells. Furthermore, HEK cells expressing both {delta}2 and GluR1, a glutamate receptor subunit forming a functional glutamate-gated ion channel, showed postsynaptic current. Deletion of the extracellular leucine/isoleucine/valine binding protein (LIVBP) domain of {delta}2 abolished the induction ability, and the LIVBP domain directly fused to a transmembrane sequence was sufficient to induce presynaptic differentiation. Furthermore, a mutant GluR1 whose LIVBP domain was replaced with the {delta}2 LIVBP domain was sufficient by itself to establish synaptic transmission. Another member of {delta} glutamate receptor family {delta}1 also induced presynaptic differentiation. Thus, the {delta} glutamate receptor subfamily can induce the differentiation of glutamatergic presynaptic terminals and contribute to the establishment of synaptic transmission.
