Two Classes of Secreted Synaptic Organizers in the Central Nervous System
Abstract
Research in the last two decades has identified many synaptic organizers in the central nervous system that directly regulate the assembly of pre- and/or postsynaptic molecules, such as synaptic vesicles, active zone proteins, and neurotransmitter receptors. They are classified into secreted factors and cell adhesion molecules, such as neurexins and neuroligins. Certain secreted factors are termed extracellular scaffolding proteins (ESPs) because they are components of the synaptic extracellular matrix and serve as a scaffold at the synaptic cleft. These include Lgi1, Cbln1, neuronal pentraxins, Hevin, thrombospondins, and glypicans. Diffusible secreted factors, such as Wnts, fibroblast growth factors, and semaphorins, tend to act from a distance. In contrast, ESPs remain at the synaptic cleft and often help synaptic adhesion and/or accumulation of postsynaptic receptors. Many fundamental questions remain about when, how, and why various synaptic organizers establish and modify the vast numbers of connections during development and throughout life.
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NPTXs are part of the family of extracellular scaffolding proteins responsible for regulating the assembly of pre- and post-synaptic compartments by recruiting post-synaptic receptors.
“They are part of the family of extracellular scaffolding proteins, responsible for regulating the assembly of pre- and post-synaptic compartments by recruiting post-synaptic receptors (Yuzaki 2018).”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Yuzaki 2018
NPTXs are synaptic organizers located in the synaptic cleft.
“NPTXs are synaptic organizers located in the synaptic cleft.”
From Neuronal pentraxins as biomarkers of synaptic activity: from physiological functions to pathological changes in neurodegeneration (2022) · cites this paper as Yuzaki 2018
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Ito, A., Miura, E., Emi, K., Matsuda, K., Iijima, T., Kondo, T., Kohda, K., Watanabe, M., & Yuzaki, M. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1030-08.2008 · Cited by 112 · see citing works
Self-citationSonic Hedgehog Expression in Corticofugal Projection Neurons Directs Cortical Microcircuit Formation
Harwell, C. C., Parker, P. R. L., Gee, S. M., Okada, A., McConnell, S. K., Kreitzer, A. C., & Kriegstein, A. R. (2012) · Neuron · doi:10.1016/j.neuron.2012.02.009 · Cited by 110 · see citing works
Seeking long‐term relationship: axon and target communicate to organize synaptic differentiation
Fox, M. A., & Umemori, H. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.03834.x · Cited by 107 · see citing works
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Iijima, T., Miura, E., Watanabe, M., & Yuzaki, M. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07202.x · Cited by 101 · see citing works
Self-citationThe C1q domain containing proteins: Where do they come from and what do they do?
Carland, T. M., & Gerwick, L. G. (2010) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2010.02.014 · Cited by 101 · see citing works
LGI1-associated epilepsy through altered ADAM23-dependent neuronal morphology
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LGI Proteins in the Nervous System
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Self-citationRole of glia in developmental synapse formation
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The C1q complement family of synaptic organizers: not just complementary
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Self-citationLGI1 Is a Nogo Receptor 1 Ligand that Antagonizes Myelin-Based Growth Inhibition
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Synaptopathy: dysfunction of synaptic function?
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Roles of Cbln1 in Non-Motor Functions of Mice
Otsuka, S., Konno, K., Abe, M., Motohashi, J., Kohda, K., Sakimura, K., Watanabe, M., & Yuzaki, M. (2016) · Journal of Neuroscience · doi:10.1523/jneurosci.0322-16.2016 · Cited by 78 · see citing works
Self-citationSatterthwaite, T. D., & Baker, J. T. (2014) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2014.10.005 · Cited by 76 · see citing works
Evolution of the Pentraxin Family: The New Entry PTX4
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Structures of C1q-like Proteins Reveal Unique Features among the C1q/TNF Superfamily
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The Cbln family of proteins interact with multiple signaling pathways
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Distinct sets of FGF receptors sculpt excitatory and inhibitory synaptogenesis
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Neuronal Pentraxins Mediate Silent Synapse Conversion in the Developing Visual System
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Cbln1 Is Essential for Interaction-Dependent Secretion of Cbln3
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Localization of the Extracellular Matrix Protein SC1 to Synapses in the Adult Rat Brain
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Target-Derived Matricryptins Organize Cerebellar Synapse Formation Through α3β1 Integrins
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Wnt signalling tunes neurotransmitter release by directly targeting Synaptotagmin-1
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Neurogenesis is enhanced and mossy fiber sprouting arises in FGF7-deficient mice during development
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The LGI1–ADAM22 protein complex in synaptic transmission and synaptic disorders
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Self-citationComparison of Cbln1 and Cbln2 functions using transgenic and knockout mice
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Selective synaptic targeting of the excitatory and inhibitory presynaptic organizers, FGF22 and FGF7
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Postsynaptic SDC2 induces transsynaptic signaling via FGF22 for bidirectional synaptic formation
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Structure, Function, and Pharmacology of Glutamate Receptor Ion Channels
Hansen, K. B., Wollmuth, L. P., Bowie, D., Furukawa, H., Menniti, F. S., Sobolevsky, A. I., Swanson, G. T., Swanger, S. A., Greger, I. H., Nakagawa, T., et al. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000131 · Cited by 686 · see citing works
The cell biology of synapse formation
Südhof, T. C. (2021) · Journal of Cell Biology · doi:10.1083/jcb.202103052 · Cited by 358 · see citing works
Shaping Synapses by the Neural Extracellular Matrix
Ferrer-Ferrer, M., & Dityatev, A. (2018) · Frontiers in Neuroanatomy · doi:10.3389/fnana.2018.00040 · Cited by 169 · see citing works
Gómez de San José, N., Massa, F., Halbgebauer, S., Oeckl, P., Steinacker, P., & Otto, M. (2022) · Journal of Neural Transmission · doi:10.1007/s00702-021-02411-2 · Cited by 112 · see citing works
Neurexin‐β mediates the synaptogenic activity of amyloid precursor protein
Cvetkovska, V., Ge, Y., Xu, Q., Li, S., Zhang, P., & Craig, A. M. (2022) · The Journal of Neuroscience · doi:10.1523/jneurosci.0511-21.2022 · Cited by 17 · see citing works
- Authors
- Yuzaki, M.
- Affiliations
- Keio University (JP)
- Corresponding author
- Yuzaki, Michisuke
- ORCID
- Yuzaki, Michisuke
- Venue
- Annual Review of Physiology
- Publisher
- Annual Reviews
- Published
- 2018-02-10
- Volume
- 80
- Issue
- 1
- Pages
- 243-262
- ISSN
- 0066-4278 (ISSN-L)
- 1545-1585
- OpenAlex
- W2622842747
- Cited by
- 125
- References
- 131
- Citations by year
- 2026: 12 · 2025: 18 · 2024: 11 · 2023: 16 · 2022: 12 · 2021: 21 · 2020: 25 · 2019: 5 · 2018: 5
- FWCI
- 1.18
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annual Review of Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Japan Society for the Promotion of Science (15H05772)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- synaptic organizer, secreted factors, synaptic cleft, synaptic adhesion, synaptic vesicles, active zone proteins, neurexin, neuroligins, LGI1, Cbln1, hevin, thrombospondin, glypicans, Wnt, fibroblast growth factor, semaphorins, synaptic development, synaptic plasticity
- MeSH terms
- Pentraxins, Animals, Brain, C-Reactive Protein, Humans, Nerve Tissue Proteins, Neuronal Plasticity, Protein Precursors, Spinal Cord, Synapses, Thrombospondins, Wnt Proteins
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