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Postsynaptic glutamate receptor delta family contributes to presynaptic terminal differentiation and establishment of synaptic transmission.

ABSTRACT: 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 delta2 subunit (delta2), 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 delta2 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 delta2 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 delta2 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 delta2 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 delta2 LIVBP domain was sufficient by itself to establish synaptic transmission. Another member of delta glutamate receptor family delta1 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.

SUBMITTER: Kuroyanagi T

PROVIDER: S-EPMC2660731 | biostudies-literature | 2009 Mar

REPOSITORIES: biostudies-literature

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Postsynaptic glutamate receptor delta family contributes to presynaptic terminal differentiation and establishment of synaptic transmission.

Kuroyanagi Tomoaki T Yokoyama Marie M Hirano Tomoo T

Proceedings of the National Academy of Sciences of the United States of America 20090303 12

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 delta2 subunit (delta2), 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 delta2 in synapse formation using culture preparations. First, we found that the size and number of GN presynaptic termi ...[more]

PMID: 19258455

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Project description:Activation of several subtypes of glutamate receptors contributes to changes in postsynaptic calcium concentration at hippocampal synapses, resulting in various types of changes in synaptic strength. Thus, while activation of NMDA receptors has been shown to be critical for long-term potentiation (LTP) and long term depression (LTD) of synaptic transmission, activation of metabotropic glutamate receptors (mGluRs) has been linked to either LTP or LTD. While it is generally admitted that dynamic changes in postsynaptic calcium concentration represent the critical elements to determine the direction and amplitude of the changes in synaptic strength, it has been difficult to quantitatively estimate the relative contribution of the different types of glutamate receptors to these changes under different experimental conditions. Here we present a detailed model of a postsynaptic glutamatergic synapse that incorporates ionotropic and mGluR type I receptors, and we use this model to determine the role of the different receptors to the dynamics of postsynaptic calcium with different patterns of presynaptic activation. Our modeling framework includes glutamate vesicular release and diffusion in the cleft and a glutamate transporter that modulates extracellular glutamate concentration. Our results indicate that the contribution of mGluRs to changes in postsynaptic calcium concentration is minimal under basal stimulation conditions and becomes apparent only at high frequency of stimulation. Furthermore, the location of mGluRs in the postsynaptic membrane is also a critical factor, as activation of distant receptors contributes significantly less to calcium dynamics than more centrally located ones. These results confirm the important role of glutamate transporters and of the localization of mGluRs in postsynaptic sites in their signaling properties, and further strengthen the notion that mGluR activation significantly contributes to postsynaptic calcium dynamics only following high-frequency stimulation. They also provide a new tool to analyze the interactions between metabotropic and ionotropic glutamate receptors.

Dataset Information

Postsynaptic glutamate receptor delta family contributes to presynaptic terminal differentiation and establishment of synaptic transmission.

Publications

Postsynaptic glutamate receptor delta family contributes to presynaptic terminal differentiation and establishment of synaptic transmission.

Similar Datasets

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