Essential functions of synapsins I and II in synaptic vesicle regulation
Abstract
Synaptic vesicles are coated by synapsins, phosphoproteins that account for 9% of the vesicle protein. To analyse the functions of these proteins, we have studied knockout mice lacking either synapsin I, synapsin II, or both. Mice lacking synapsins are viable and fertile with no gross anatomical abnormalities, but experience seizures with a frequency proportional to the number of mutant alleles. Synapsin-II and double knockouts, but not synapsin-I knockouts, exhibit decreased post-tetanic potentiation and severe synaptic depression upon repetitive stimulation. Intrinsic synaptic-vesicle membrane proteins, but not peripheral membrane proteins or other synaptic proteins, are slightly decreased in individual knockouts and more severely reduced in double knockouts, as is the number of synaptic vesicles. Thus synapsins are not required for neurite outgrowth, synaptogenesis or the basic mechanics of synaptic vesicle traffic, but are essential for accelerating this traffic during repetitive stimulation. The phenotype of the synapsin knockouts could be explained either by deficient recruitment of synaptic vesicles to the active zone, or by impaired maturation of vesicles at the active zone, both of which could lead to a secondary destabilization of synaptic vesicles.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Mutations in synapsins, Munc13, and RIMs alter short-term plasticity in a manner independent of the first two sets of mechanisms.
“Mutations in several proteins associated with the release machinery alter short-term plasticity in a manner independent of the first two sets of mechanisms, for example mutations in synapsins (Rosahl et al., 1995), Munc13 (Augustin et al., 1999), and RIMs (Schoch et al., 2002).”
From The Presynaptic Active Zone (2012) · cites this paper as Rosahl et al., 1995
Cited by
Sorted by citations
Short-Term Synaptic Plasticity
Zucker, R. S., & Regehr, W. G. (2002) · Annual Review of Physiology · doi:10.1146/annurev.physiol.64.092501.114547 · Cited by 5,068 · see citing works
Südhof, T. C. (2004) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.26.041002.131412 · Cited by 2,491 · see citing works
Self-citationSüdhof, T. C. (2012) · Neuron · doi:10.1016/j.neuron.2012.06.012 · Cited by 1,062 · see citing works
Self-citationMcKernan, R. M., Rosahl, T. W., Reynolds, D. S., Sur, C., Wafford, K. A., Atack, J. R., Farrar, S., Myers, J., Cook, G., Ferris, P., et al. (2000) · Nature Neuroscience · doi:10.1038/75761 · Cited by 944 · see citing works
Self-citationMirnics, K., Middleton, F. A., Marquez, A., Lewis, D. A., & Levitt, P. (2000) · Neuron · doi:10.1016/s0896-6273(00)00085-4 · Cited by 882 · see citing works
Cabin, D. E., Shimazu, K., Murphy, D., Cole, N. B., Gottschalk, W., McIlwain, K. L., Orrison, B., Chen, A., Ellis, C. E., Paylor, R., et al. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-20-08797.2002 · Cited by 865 · see citing works
α-Neurexins couple Ca2+ channels to synaptic vesicle exocytosis
Missler, M., Zhang, W., Rohlmann, A., Kattenstroth, G., Hammer, R. E., Gottmann, K., & Südhof, T. C. (2003) · Nature · doi:10.1038/nature01755 · Cited by 699 · see citing works
Self-citationThe synapsins: Key actors of synapse function and plasticity
Cesca, F., Baldelli, P., Valtorta, F., & Benfenati, F. (2010) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2010.04.006 · Cited by 654 · see citing works
RIM1α forms a protein scaffold for regulating neurotransmitter release at the active zone
Schoch, S., Castillo, P. E., Jo, T., Mukherjee, K., Geppert, M., Wang, Y., Schmitz, F., Malenka, R. C., & Südhof, T. C. (2002) · Nature · doi:10.1038/415321a · Cited by 579 · see citing works
Self-citationThe Cell Biology of Synaptic Plasticity
Ho, V. M., Lee, J.-A., & Martin, K. C. (2011) · Science · doi:10.1126/science.1209236 · Cited by 573 · see citing works
Synapsins as Regulators of Neurotransmitter Release
Hilfiker, S., Pieribone, V. A., Czernik, A. J., Kao, H.-T., Augustine, G. J., & Greengard, P. (1999) · Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rstb.1999.0378 · Cited by 537 · see citing works
Short-Term Presynaptic Plasticity
Regehr, W. G. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a005702 · Cited by 482 · see citing works
Double-knockout mice for α- and β-synucleins: Effect on synaptic functions
Chandra, S., Fornai, F., Kwon, H.-B., Yazdani, U., Atasoy, D., Liu, X., Hammer, R. E., Battaglia, G., German, D. C., Castillo, P. E., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0406283101 · Cited by 438 · see citing works
Self-citationAbnormal neurotransmission in mice lacking synaptic vesicle protein 2A (SV2A)
Crowder, K. M., Gunther, J. M., Jones, T. A., Hale, B. D., Zhang, H. Z., Peterson, M. R., Scheller, R. H., Chavkin, C., & Bajjalieh, S. M. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.26.15268 · Cited by 415 · see citing works
Xu, J., Mashimo, T., & Südhof, T. C. (2007) · Neuron · doi:10.1016/j.neuron.2007.05.004 · Cited by 336 · see citing works
Self-citationSynaptophysin, a major synaptic vesicle protein, is not essential for neurotransmitter release
McMahon, H. T., Bolshakov, V. Y., Janz, R., Hammer, R. E., Siegelbaum, S. A., & Südhof, T. C. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.10.4760 · Cited by 262 · see citing works
Self-citationZhu, L.-Q., Wang, S.-H., Liu, D., Yin, Y.-Y., Tian, Q., Wang, X.-C., Wang, Q., Chen, J.-G., & Wang, J.-Z. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3321-07.2007 · Cited by 234 · see citing works
Ho, A., & Südhof, T. C. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308655100 · Cited by 224 · see citing works
Self-citationIdentification of a mutation in synapsin I, a synaptic vesicle protein, in a family with epilepsy
Garcia, C. C., Blair, H. J., Seager, M., Coulthard, A., Tennant, S., Buddles, M., Curtis, A., & Goodship, J. A. (2004) · Journal of Medical Genetics · doi:10.1136/jmg.2003.013680 · Cited by 205 · see citing works
Lipid Metabolism Crosstalk in the Brain: Glia and Neurons
Barber, C. N., & Raben, D. M. (2019) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2019.00212 · Cited by 188 · see citing works
A molecular pathway of neurodegeneration linking α-synuclein to ApoE and Aβ peptides
Gallardo, G., Schlüter, O. M., & Südhof, T. C. (2008) · Nature Neuroscience · doi:10.1038/nn2058 · Cited by 145 · see citing works
Self-citationTreccani, G., Musazzi, L., Perego, C., Milanese, M., Nava, N., Bonifacino, T., Lamanna, J., Malgaroli, A., Drago, F., Racagni, G., et al. (2014) · Molecular Psychiatry · doi:10.1038/mp.2014.5 · Cited by 133 · see citing works
Cruceanu, C., Alda, M., Nagy, C., Freemantle, E., Rouleau, G. A., & Turecki, G. (2013) · International Journal of Neuropsychopharmacology · doi:10.1017/s1461145712000363 · Cited by 93 · see citing works
Recent advances in gene therapy for neurodevelopmental disorders with epilepsy
Turner, T. J., Zourray, C., Schorge, S., & Lignani, G. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15168 · Cited by 71 · see citing works
Differential distributions of novel synaptotagmins: Comparison to synapsins
Ullrich, B., & Südhof, T. C. (1995) · Neuropharmacology · doi:10.1016/0028-3908(95)00132-p · Cited by 61 · see citing works
Self-citationCentral presynaptic terminals are enriched in ATP but the majority lack mitochondria
Chavan, V., Willis, J., Walker, S. K., Clark, H. R., Liu, X., Fox, M. A., Srivastava, S., & Mukherjee, K. (2015) · PLoS ONE · doi:10.1371/journal.pone.0125185 · Cited by 52 · see citing works
The effects of sevoflurane anesthesia on rat brain proteins: a proteomic time-course analysis
Kalenka, A., Hinkelbein, J., Feldmann, R. E., Kuschinsky, W., Waschke, K. F., & Maurer, M. H. (2007) · Anesthesia & Analgesia · doi:10.1213/01.ane.0000260799.37107.e6 · Cited by 47 · see citing works
Counotte, D. S., Li, K. W., Wortel, J., Gouwenberg, Y., Van Der Schors, R. C., Smit, A. B., & Spijker, S. (2010) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2010.07404.x · Cited by 47 · see citing works
- Authors
- Rosahl, T. W., Spillane, D., Missler, M., Herz, J., Selig, D. K., Wolff, J. R., Hammer, R. E., Malenka, R. C., & Südhof, T. C.
- Affiliations
- The University of Texas Southwestern Medical Center (US)
- University of California, San Francisco (US)
- Howard Hughes Medical Institute (US)
- University of Göttingen (DE)
- ORCID
- Venue
- Nature
- Published
- 1995-06
- Volume
- 375
- Issue
- 6531
- Pages
- 488-493
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2022046189
- Cited by
- 719
- References
- 0
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 13 · 2023: 28 · 2022: 19 · 2021: 13 · 2020: 11 · 2019: 17 · 2018: 11 · 2017: 15 · 2016: 9 · 2015: 19 · 2014: 21 · 2013: 18 · 2012: 41
- FWCI
- 14.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- synapsin I, synapsin II, synaptic vesicles, knockout mice, seizures, post-tetanic potentiation, synaptic depression, repetitive stimulation, active zone, vesicle maturation, synaptogenesis
- MeSH terms
- Animals, Base Sequence, Brain, Female, Male, Membrane Fusion, Molecular Sequence Data, Synaptic Transmission, Oligodeoxyribonucleotides, Phenotype, Seizures, Synaptic Vesicles, Immunoblotting, Neurites, Synapsins, Mice, Knockout, Neurotransmitter Agents, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
