2022
DOI: 10.1038/s41467-022-29751-1
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Teneurins assemble into presynaptic nanoclusters that promote synapse formation via postsynaptic non-teneurin ligands

Abstract: Extensive studies concluded that homophilic interactions between pre- and postsynaptic teneurins, evolutionarily conserved cell-adhesion molecules, encode the specificity of synaptic connections. However, no direct evidence is available to demonstrate that teneurins are actually required on both pre- and postsynaptic neurons for establishing synaptic connections, nor is it known whether teneurins are localized to synapses. Using super-resolution microscopy, we demonstrate that Teneurin-3 assembles into presyna… Show more

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Cited by 27 publications
(42 citation statements)
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“…Similarly, while the overlap of teneurin is lowest with inhibitory postsynaptic sites (9%), paralogue localisation to excitatory postsynaptic sites is higher. The double-labelling of hippocampal sections for Tenm3 and synaptic markers in a recent study also shows that Tenm3 is more likely to be co-localised with excitatory synaptic markers ( Zhang et al, 2022 ). On average, the total (excitatory and inhibitory) combined proportion of teneurin localised at either presynaptic (28%) or postsynaptic sites (29.5%) is almost equivalent, consistent for proteins that form homophilic complexes across the synaptic cleft.…”
Section: Discussionmentioning
confidence: 88%
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“…Similarly, while the overlap of teneurin is lowest with inhibitory postsynaptic sites (9%), paralogue localisation to excitatory postsynaptic sites is higher. The double-labelling of hippocampal sections for Tenm3 and synaptic markers in a recent study also shows that Tenm3 is more likely to be co-localised with excitatory synaptic markers ( Zhang et al, 2022 ). On average, the total (excitatory and inhibitory) combined proportion of teneurin localised at either presynaptic (28%) or postsynaptic sites (29.5%) is almost equivalent, consistent for proteins that form homophilic complexes across the synaptic cleft.…”
Section: Discussionmentioning
confidence: 88%
“…It remains to be seen whether teneurin interactions in trans with other teneurins (either heterophilic or homophilic) are able to contribute to synaptic specificity in the same way in vertebrates as the orthologues in Drosophila ( Hong et al, 2012 ; Mosca et al, 2012 ). Indeed, recent observations suggest that while teneurins are expressed both pre- and postsynaptically, they possibly function primarily as presynaptic adhesion molecules that interact with other postsynaptic ligands such as LPHNs and may not actually be required for postsynaptic interactions themselves ( Zhang et al, 2022 ). This is because only the pre- but not postsynaptic deletions of Tenm3 and Tenm4 in the medial entorhinal cortex produced impairments in synaptic connectivity in mice ( Zhang et al, 2022 ).…”
Section: Discussionmentioning
confidence: 99%
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“…[7,20] Teneurins appear to exclusively regulate the presynaptic properties of specific neural circuits encompassing hippocampal CA1 pyramidal neurons. [21] In this article, we will focus on the trans-synaptic actions of Nrxns at excitatory and inhibitory synapses via cerebellins, and those of PTPσ (an LAR-RPTP) at excitatory synapses (Figure 1A, B; Table 1). We will also highlight the putative trans-synaptic function of amyloid precursor protein (APP) in regulating postsynaptic γ-aminobutyric acid type A receptor (GABA A R)-mediated synaptic inhibition in the hippocampus (Figure 1C; Table 1).…”
Section: Presynaptic Adhesion Molecules Regulate the Specific Propert...mentioning
confidence: 99%
“…We estimate that at least 20 SAMs distributed over 10 gene families follow this pattern of driving synapse organization when overexpressed in non-neuronal cells that are co-cultured with neurons, but that are not essential for synapse formation in an in vivo setting. In contrast to these groups of SAMs, two families of adhesion-GPCRs, BAIs and latrophilins, and their ligands were found to be essential for synapse formation in vivo [33][34][35][36][37][38] . Viewed together, these results suggest that SAMs fall into two classes, those that 'make' a synapse such as Latrophilins and Bai's, and those that 'shape' a synapse, such as Nlgns and Nrxns 1 .…”
Section: Introductionmentioning
confidence: 96%