Dataset Information

Dynamics of the mouse brain cortical synaptic proteome during postnatal brain development

ABSTRACT: Development of the brain involves the formation and maturation of numerous synapses. This process requires prominent changes of the synaptic proteome and potentially involves thousands of different proteins at every synapse. To date the proteome analysis of synapse development has been studied sparsely. Here, we analyzed the cortical synaptic membrane proteome of juvenile [postnatal day 9 (P9), P15, P21, P27], adolescent (P35) and different adult ages (P70, P140, P280) of C57Bl6/J mice. Using a quantitative proteomics workflow we quantified 1560 proteins of which 696 showed statistically significant differences over time. Proteins of the presynaptic active-zone and postsynaptic element showed increased levels over time; proteins involved in protein synthesis or neurite outgrowth generally decreased in abundance. In several cases, proteins from a single functional molecular entity, e.g., subunits of the NMDA receptor, showed profound differences in their temporal regulation, which may reflect specific synaptic development features of connectivity, strength and plasticity.

INSTRUMENT(S): 4800 Proteomics Analyzer

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Pim van Nierop

LAB HEAD: Ka Wan Li

PROVIDER: PXD004129 | Pride | 2018-10-26

REPOSITORIES: Pride

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Publications

Dynamics of the mouse brain cortical synaptic proteome during postnatal brain development.

Gonzalez-Lozano Miguel A MA Klemmer Patricia P Gebuis Titia T Hassan Chopie C van Nierop Pim P van Kesteren Ronald E RE Smit August B AB Li Ka Wan KW

Scientific reports 20161017

Development of the brain involves the formation and maturation of numerous synapses. This process requires prominent changes of the synaptic proteome and potentially involves thousands of different proteins at every synapse. To date the proteome analysis of synapse development has been studied sparsely. Here, we analyzed the cortical synaptic membrane proteome of juvenile postnatal days 9 (P9), P15, P21, P27, adolescent (P35) and different adult ages P70, P140 and P280 of C57Bl6/J mice. Using a ...[more]

PMID: 27748445

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Project description:The prevailing model behind synapse development and specificity is that a multitude of adhesion molecules engage in transsynaptic interactions to induce pre- and post-synaptic assembly. How these extracellular interactions translate into intracellular signal transduction for synaptic assembly remains unclear. One such complex formed by immunoglobulin superfamily member 21 (IgSF21) and neurexin2α regulates GABAergic synapse development in the mouse brain, but the precise molecular mechanisms underlying this activity remain unclear. Here, we reveal that the interaction between presynaptic Nrxn2α and postsynaptic IgSF21 is a high-affinity receptor-ligand interaction and identify a binding interface in the IgSF21-Nrxn2α complex. Despite being expressed in both dendritic and somatic regions, IgSF21 preferentially regulates dendritic GABAergic presynaptic differentiation whereas another canonical Nrxn ligand, neuroligin2 (Nlgn2), regulates primarily perisomatic presynaptic differentiation. To explore mechanisms that could underly this compartment specificity, we targeted multiple signaling pathways pharmacologically while monitoring the synaptogenic activity of IgSF21 and Nlgn2. Interestingly, both IgSF21 and Nlgn2 require c-jun N-terminal kinase (JNK)-mediated signaling, whereas Nlgn2, but not IgSF21, additionally requires CaMKII and Src kinase activity. JNK inhibition diminished de novo presynaptic differentiation without affecting the maintenance of formed synapses. We further found that Nrxn2α knockout brains exhibit altered synaptic JNK activity in a sex-specific fashion, suggesting functional linkage between Nrxns and JNK in vivo. Thus, our study elucidates the structural and functional relationship of IgSF21 with Nrxn2α and distinct signaling pathways for IgSF21 and Nlgn downstream of Nrxn2α. We therefore propose a revised hypothesis that Nrxns act as molecular hubs to specify synaptic properties not only through their multiple extracellular ligands but also through distinct intracellular signaling pathways of these ligands.

Dataset Information

Dynamics of the mouse brain cortical synaptic proteome during postnatal brain development

Publications

Dynamics of the mouse brain cortical synaptic proteome during postnatal brain development.

Similar Datasets

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