Matching of Pre- and Postsynaptic Specializations during Synaptogenesis

Lardi-Studler, Barbara; Fritschy, Jean‐Marc

doi:10.1177/1073858406296803

Cited by 45 publications

(32 citation statements)

References 79 publications

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“…2004; Li et al 2005b;Lardi-Studler and Fritschy 2007;Yu et al 2007;Yu and De Blas 2008). In this study, we show that GRIP1c4-7 and GRIP1a/b associate and interact directly with gephyrin and that both GRIP1 isoforms colocalize with gephyrin at the GABAergic post-synaptic complex, suggesting that the interaction between gephyrin and GRIP1 plays a role in GABAergic synaptic function.…”

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confidence: 75%

Gephyrin interacts with the glutamate receptor interacting protein 1 isoforms at GABAergic synapses

Charych

Serwanski

et al. 2008

Journal of Neurochemistry

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We have previously shown that the glutamate receptor interacting protein 1 (GRIP1) splice forms GRIP1a/b and GRIP1c4–7 are present at the GABAergic post‐synaptic complex. Nevertheless, the role that these GRIP1 protein isoforms play at the GABAergic post‐synaptic complex is not known. We are now showing that GRIP1c4–7 and GRIP1a/b interact with gephyrin, the main post‐synaptic scaffold protein of GABAergic and glycinergic synapses. Gephyrin coprecipitates with GRIP1c4–7 or GRIP1a/b from rat brain extracts and from extracts of human embryonic kidney 293 cells that have been cotransfected with gephyrin and one of the GRIP1 protein isoforms. Moreover, purified gephyrin binds to purified GRIP1c4–7 or GRIP1a/b, indicating that gephyrin directly interacts with the common region of these GRIP1 proteins, which includes PDZ domains 4–7. An engineered deletion construct of GRIP1a/b (GRIP1a4–7), which both contains the aforementioned common region and binds to gephyrin, targets to the post‐synaptic GABAergic complex of transfected cultured hippocampal neurons. In these hippocampal cultures, endogenous gephyrin colocalizes with endogenous GRIP1c4–7 and GRIP1a/b in over 90% of the GABAergic synapses. Double‐labeling electron microscopy immunogold reveals that in the rat brain GRIP1c4–7 and GRIP1a/b colocalize with gephyrin at the post‐synaptic complex of individual synapses. These results indicate that GRIP1c4–7 and GRIP1a/b colocalize and interact with gephyrin at the GABAergic post‐synaptic complex and suggest that this interaction plays a role in GABAergic synaptic function.

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confidence: 75%

Gephyrin interacts with the glutamate receptor interacting protein 1 isoforms at GABAergic synapses

Charych

Serwanski

et al. 2008

Journal of Neurochemistry

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“…Electrical activity exerts a key role in controlling the specificity of neurotransmitter/receptor matching, both during the developmental period and in the mature brain (1,2). Vertebrate skeletal muscle expresses five classes of neurotransmitter receptors at early developmental stages, four of which are eliminated during the achievement of the mature cholinergic phenotype.…”

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confidence: 99%

Transmitter-receptor mismatch in GABAergic synapses in the absence of activity

Cesa

Morando

Strata

2008

Proc. Natl. Acad. Sci. U.S.A.

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Competition among different axons to reach the somatodendritic region of the target neuron is an important event during development to achieve the final architecture typical of the mature brain. Trasmitter-receptor matching is a critical step for the signaling between neurons. In the cerebellar cortex, there is a persistent competition between the two glutamatergic inputs, the parallel fibers and the climbing fibers, for the innervation of the Purkinje cells. The activity of the latter input is necessary to maintain its own synaptic contacts on the proximal dendritic domain and to confine the parallel fibers in the distal one. Here, we show that climbing fiber activity also limits the distribution of the GABAergic input in the proximal domain. In addition, blocking the activity by tetrodotoxin infusion in Wistar rat cerebellum, a synapse made by GABAergic terminals onto the recently formed Purkinje cell spines appear in the proximal dendrites. The density of GABAergic terminals is increased, and unexpected double symmetric/asymmetric postsynaptic densities add to the typical symmetric phenotype of the GABAergic shaft synapses. Moreover, glutamate receptors appear in these ectopic synapses even in the absence of glutamate transmitter inside the presynaptic terminal and close to GABA receptors. These results suggest that the Purkinje cell has an intrinsic tendency to develop postsynaptic assemblies of excitatory types, including glutamate receptors, over the entire dendritic territory. GABA receptors are induced in these assemblies when contacted by GABAergic terminals, thus leading to the formation of hybrid synapses.cerebellum ͉ GABA receptor ͉ spinogenesis ͉ synaptic plasticity

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“…Most, if not all, asymmetric and symmetric synapses are excitatory and inhibitory, respectively, as they selectively express ionotropic glutamate or GABA/glycine receptors together with their specific scaffolding proteins (2). Neurochemical matching of chemical synapses is controlled by activity-dependent mechanisms (3,4), and mediated by transmembrane adhesion proteins and secreted molecules (5). The neuroligin (NL) family comprises postsynaptic adhesion molecules that form transsynaptic contacts with presynaptic neurexins (Nrxn) (6).…”

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confidence: 99%

Dopamine synapse is a neuroligin-2–mediated contact between dopaminergic presynaptic and GABAergic postsynaptic structures

Uchigashima

Ohtsuka

Kobayashi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

111

104

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Midbrain dopamine neurons project densely to the striatum and form so-called dopamine synapses on medium spiny neurons (MSNs), principal neurons in the striatum. Because dopamine receptors are widely expressed away from dopamine synapses, it remains unclear how dopamine synapses are involved in dopaminergic transmission. Here we demonstrate that dopamine synapses are contacts formed between dopaminergic presynaptic and GABAergic postsynaptic structures. The presynaptic structure expressed tyrosine hydroxylase, vesicular monoamine transporter-2, and plasmalemmal dopamine transporter, which are essential for dopamine synthesis, vesicular filling, and recycling, but was below the detection threshold for molecules involving GABA synthesis and vesicular filling or for GABA itself. In contrast, the postsynaptic structure of dopamine synapses expressed GABAergic molecules, including postsynaptic adhesion molecule neuroligin-2, postsynaptic scaffolding molecule gephyrin, and GABA A receptor α1, without any specific clustering of dopamine receptors. Of these, neuroligin-2 promoted presynaptic differentiation in axons of midbrain dopamine neurons and striatal GABAergic neurons in culture. After neuroligin-2 knockdown in the striatum, a significant decrease of dopamine synapses coupled with a reciprocal increase of GABAergic synapses was observed on MSN dendrites. This finding suggests that neuroligin-2 controls striatal synapse formation by giving competitive advantage to heterologous dopamine synapses over conventional GABAergic synapses. Considering that MSN dendrites are preferential targets of dopamine synapses and express high levels of dopamine receptors, dopamine synapse formation may serve to increase the specificity and potency of dopaminergic modulation of striatal outputs by anchoring dopamine release sites to dopamine-sensing targets.dopamine synapse | neuroligin-2 | medium spiny neuron | striatum C hemical synapses comprise presynaptic machinery for transmitter release and postsynaptic machinery for receptor-mediated signal transduction in a neurochemically matched manner. They are classified into Gray type-I and type-II synapses by asymmetric or symmetric membrane density, respectively, of the preand postsynaptic structures (1). Most, if not all, asymmetric and symmetric synapses are excitatory and inhibitory, respectively, as they selectively express ionotropic glutamate or GABA/glycine receptors together with their specific scaffolding proteins (2). Neurochemical matching of chemical synapses is controlled by activity-dependent mechanisms (3, 4), and mediated by transmembrane adhesion proteins and secreted molecules (5). The neuroligin (NL) family comprises postsynaptic adhesion molecules that form transsynaptic contacts with presynaptic neurexins (Nrxn) (6). Of note, NL1 and NL2 are selectively expressed at glutamatergic and GABAergic synapses, respectively (7,8), and are required for activity-dependent specification of the corresponding synapses (9).Midbrain dopamine neurons project densely to the striat...

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Matching of Pre- and Postsynaptic Specializations during Synaptogenesis

Cited by 45 publications

References 79 publications

Gephyrin interacts with the glutamate receptor interacting protein 1 isoforms at GABAergic synapses

Gephyrin interacts with the glutamate receptor interacting protein 1 isoforms at GABAergic synapses

Transmitter-receptor mismatch in GABAergic synapses in the absence of activity

Dopamine synapse is a neuroligin-2–mediated contact between dopaminergic presynaptic and GABAergic postsynaptic structures

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