ArticleProceedings of the National Academy of Sciences of the United States of America2021
Multiple signaling pathways are essential for synapse formation induced by synaptic adhesion molecules.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 48 citations in OpenAlex.
- Synapse-like specializations at dopamine release sites orchestrate efficient and precise neuromodulatory signaling.Science advances · 2026Article
- TRIM25 facilitates mitochondrial dysfunction and extracellular matrix degradation by enhancing USP7-driven ENO1 deubiquitination during intervertebral disc degeneration.Clinical and translational medicine · 2026Article
- PTEN Subcellular Localization Dictates Function.bioRxiv : the preprint server for biology · 2026Article
- Phase separation instead of binding strength determines target specificities of MAGUKs.Nature chemical biology · 2026Article
- Synaptic Cell Adhesion: A Functional Perspective.Advances in neurobiology · 2026Review
- Synaptic Cell Adhesion: A Structural Perspective.Advances in neurobiology · 2026Review
- Roles of NRXN1 in neuropsychiatric disorders: from genetic lesion to molecular mechanism.Frontiers in neuroscience · 2026Review
- High-content image-based pooled screens reveal regulators of synaptogenesis.Cell reports · 2025Article
- Perturbed synaptic adhesion molecules signaling in neurodevelopmental disorders: The impact of metal neurotoxicity.Ibrain · 2025Review
- Synaptic Gα12/13 signaling establishes hippocampal PV inhibitory circuits.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Cell Adhesion Molecule Signaling at the Synapse: Beyond the Scaffold.Cold Spring Harbor perspectives in biology · 2024Review
- Postsynaptic receptors regulate presynaptic transmitter stability through transsynaptic bridges.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Patronin regulates presynaptic microtubule organization and neuromuscular junction development iniScience · 2024Article
- Neuroligin-1 dependent phosphotyrosine signaling in excitatory synapse differentiation.Frontiers in molecular neuroscience · 2024Article
- Structural and functional characterization of the IgSF21-neurexin2α complex and its related signaling pathways in the regulation of inhibitory synapse organization.Frontiers in molecular neuroscience · 2024Article
- Integrative analysis of long noncoding RNAs dysregulation and synapse-associated ceRNA regulatory axes in autism.Translational psychiatry · 2023Article
- SAD-1 kinase controls presynaptic phase separation by relieving SYD-2/Liprin-α autoinhibition.PLoS biology · 2023Article
- Neurexin-2 restricts synapse numbers and restrains the presynaptic release probability by an alternative splicing-dependent mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Engineered adhesion molecules drive synapse organization.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Functional Diversity of Neuronal Cell Adhesion and Recognition Molecule L1CAM through Proteolytic Cleavage.Cells · 2022Review
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Authors and funding
3 authors at 1 institution in 1 country.
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Abstract
Little is known about the cellular signals that organize synapse formation. To explore what signaling pathways may be involved, we employed heterologous synapse formation assays in which a synaptic adhesion molecule expressed in a nonneuronal cell induces pre- or postsynaptic specializations in cocultured neurons. We found that interfering pharmacologically with microtubules or actin filaments impaired heterologous synapse formation, whereas blocking protein synthesis had no effect. Unexpectedly, pharmacological inhibition of c-jun N-terminal kinases (JNKs), protein kinase-A (PKA), or AKT kinases also suppressed heterologous synapse formation, while inhibition of other tested signaling pathways-such as MAP kinases or protein kinase C-did not alter heterologous synapse formation. JNK and PKA inhibitors suppressed formation of both pre- and postsynaptic specializations, whereas AKT inhibitors impaired formation of post- but not presynaptic specializations. To independently test whether heterologous synapse formation depends on AKT signaling, we targeted PTEN, an enzyme that hydrolyzes phosphatidylinositol 3-phosphate and thereby prevents AKT kinase activation, to postsynaptic sites by fusing PTEN to Homer1. Targeting PTEN to postsynaptic specializations impaired heterologous postsynaptic synapse formation induced by presynaptic adhesion molecules, such as neurexins and additionally decreased excitatory synapse function in cultured neurons. Taken together, our results suggest that heterologous synapse formation is driven via a multifaceted and multistage kinase network, with diverse signals organizing pre- and postsynaptic specializations.
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