A Syd-1 homologue regulates pre- and postsynaptic maturation in Drosophila
Open accessAbstract
Active zones (AZs) are presynaptic membrane domains mediating synaptic vesicle fusion opposite postsynaptic densities (PSDs). At the Drosophila neuromuscular junction, the ELKS family member Bruchpilot (BRP) is essential for dense body formation and functional maturation of AZs. Using a proteomics approach, we identified Drosophila Syd-1 (DSyd-1) as a BRP binding partner. In vivo imaging shows that DSyd-1 arrives early at nascent AZs together with DLiprin-α, and both proteins localize to the AZ edge as the AZ matures. Mutants in dsyd-1 form smaller terminals with fewer release sites, and release less neurotransmitter. The remaining AZs are often large and misshapen, and ectopic, electron-dense accumulations of BRP form in boutons and axons. Furthermore, glutamate receptor content at PSDs increases because of excessive DGluRIIA accumulation. The AZ protein DSyd-1 is needed to properly localize DLiprin-α at AZs, and seems to control effective nucleation of newly forming AZs together with DLiprin-α. DSyd-1 also organizes trans-synaptic signaling to control maturation of PSD composition independently of DLiprin-α.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Proteins related to C. elegans SYD-1 are important for the assembly of active zones in invertebrates.
“In addition to these five core active zone proteins, piccolo and bassoon (two large homologous proteins) are associated in vertebrates with active zones (tom Dieck et al., 1998; Wang et al., 1999; Fenster et al., 2000; Limbach et al., 2011), and proteins related to C. elegans SYD-1 are important for the assembly of active zones in invertebrates (Hallam et al., 2002; Patel et al., 2006; Owald et al”
From The Presynaptic Active Zone (2012) · cites this paper as Owald et al., 2010
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Neuroligins and neurexins link synaptic function to cognitive disease
Südhof, T. C. (2008) · Nature · doi:10.1038/nature07456 · Cited by 1,849 · see citing works
SYD-2 Liprin-α organizes presynaptic active zone formation through ELKS
Dai, Y., Taru, H., Deken, S. L., Grill, B., Ackley, B., Nonet, M. L., & Jin, Y. (2006) · Nature Neuroscience · doi:10.1038/nn1808 · Cited by 218 · see citing works
Hallam, S. J., Goncharov, A., McEwen, J., Baran, R., & Jin, Y. (2002) · Nature Neuroscience · doi:10.1038/nn959 · Cited by 118 · see citing works
Flagged first, then by citations
Research works printed but not linked: 46
- Betschinger J. Mechtler K. Knoblich J.A. 2003 The Par complex directs asymmetric cell division by phosphorylating the cytoskeletal protein Lgl. Nature. 422: 326– 330 10.1038/nature01486 12629552 · DOI
- Collins C.A. DiAntonio A. 2007 Synaptic development: insights from Drosophila. Curr. Opin. Neurobiol. 17: 35– 42 10.1016/j.conb.2007.01.001 17229568 · DOI · Paper page
- Daniels R.W. Collins C.A. Gelfand M.V. Dant J. Brooks E.S. Krantz D.E. DiAntonio A. 2004 Increased expression of the Drosophila vesicular glutamate transporter leads to excess glutamate release and a compensatory decrease in quantal content. J. Neurosci. 24: 10466– 10474 10.1523/JNEUROSCI.3001-04.2004 15548661 PMC6730318 · DOI
- DiAntonio A. 2006 Glutamate receptors at the Drosophila neuromuscular junction. Int. Rev. Neurobiol. 75: 165– 179 10.1016/S0074-7742(06)75008-5 17137928 · DOI
- Eissenberg J.C. Wong M. Chrivia J.C. 2005 Human SRCAP and Drosophila melanogaster DOM are homologs that function in the notch signaling pathway. Mol. Cell. Biol. 25: 6559– 6569 10.1128/MCB.25.15.6559-6569.2005 16024792 PMC1190335 · DOI
- Fiala J.C. 2005 Reconstruct: a free editor for serial section microscopy. J. Microsc. 218: 52– 61 10.1111/j.1365-2818.2005.01466.x 15817063 · DOI
- Fouquet W. Owald D. Wichmann C. Mertel S. Depner H. Dyba M. Hallermann S. Kittel R.J. Eimer S. Sigrist S.J. 2009 Maturation of active zone assembly by Drosophila Bruchpilot. J. Cell Biol. 186: 129– 145 19596851 PMC2712991
- Giagtzoglou N. Mahoney T. Yao C.K. Bellen H.J. 2009 Rab3 GTPase lands Bruchpilot. Neuron. 64: 595– 597 10.1016/j.neuron.2009.11.029 20005815 PMC5687091 · DOI
- Graf E.R. Daniels R.W. Burgess R.W. Schwarz T.L. DiAntonio A. 2009 Rab3 dynamically controls protein composition at active zones. Neuron. 64: 663– 677 10.1016/j.neuron.2009.11.002 20005823 PMC2796257 · DOI
- Jin Y. Garner C.C. 2008 Molecular mechanisms of presynaptic differentiation. Annu. Rev. Cell Dev. Biol. 24: 237– 262 10.1146/annurev.cellbio.23.090506.123417 18588488 · DOI
- Johnson E.L. III Fetter R.D. Davis G.W. 2009 Negative regulation of active zone assembly by a newly identified SR protein kinase. PLoS Biol. 7: e1000193 10.1371/journal.pbio.1000193 19771148 PMC2737616 · DOI
- Kaufmann N. DeProto J. Ranjan R. Wan H. Van Vactor D. 2002 Drosophila liprin-alpha and the receptor phosphatase Dlar control synapse morphogenesis. Neuron. 34: 27– 38 10.1016/S0896-6273(02)00643-8 11931739 · DOI
- Kittel R.J. Wichmann C. Rasse T.M. Fouquet W. Schmidt M. Schmid A. Wagh D.A. Pawlu C. Kellner R.R. Willig K.I. 2006 Bruchpilot promotes active zone assembly, Ca2+ channel clustering, and vesicle release. Science. 312: 1051– 1054 10.1126/science.1126308 16614170 · DOI · Paper page
- Leiss F. Koper E. Hein I. Fouquet W. Lindner J. Sigrist S. Tavosanis G. 2009 Characterization of dendritic spines in the Drosophila central nervous system. Dev. Neurobiol. 69: 221– 234 10.1002/dneu.20699 19160442 · DOI
- Li J. Ashley J. Budnik V. Bhat M.A. 2007 Crucial role of Drosophila neurexin in proper active zone apposition to postsynaptic densities, synaptic growth, and synaptic transmission. Neuron. 55: 741– 755 10.1016/j.neuron.2007.08.002 17785181 PMC2039911 · DOI
- Liebl F.L. Chen K. Karr J. Sheng Q. Featherstone D.E. 2005 Increased synaptic microtubules and altered synapse development in Drosophila sec8 mutants. BMC Biol. 3: 27 10.1186/1741-7007-3-27 16351720 PMC1326216 · DOI
- Luo L. Lee T. Tsai L. Tang G. Jan L.Y. Jan Y.N. 1997 Genghis Khan (Gek) as a putative effector for Drosophila Cdc42 and regulator of actin polymerization. Proc. Natl. Acad. Sci. USA. 94: 12963– 12968 10.1073/pnas.94.24.12963 9371783 PMC24246 · DOI
- Mahr A. Aberle H. 2006 The expression pattern of the Drosophila vesicular glutamate transporter: a marker protein for motoneurons and glutamatergic centers in the brain. Gene Expr. Patterns. 6: 299– 309 10.1016/j.modgep.2005.07.006 16378756 · DOI
- Margeta M.A. Shen K. Grill B. 2008 Building a synapse: lessons on synaptic specificity and presynaptic assembly from the nematode C. elegans. Curr. Opin. Neurobiol. 18: 69– 76 10.1016/j.conb.2008.04.003 18538560 PMC3849022 · DOI
- Marrus S.B. Portman S.L. Allen M.J. Moffat K.G. DiAntonio A. 2004 Differential localization of glutamate receptor subunits at the Drosophila neuromuscular junction. J. Neurosci. 24: 1406– 1415 10.1523/JNEUROSCI.1575-03.2004 14960613 PMC6730334 · DOI
- Miller K.E. DeProto J. Kaufmann N. Patel B.N. Duckworth A. Van Vactor D. 2005 Direct observation demonstrates that Liprin-alpha is required for trafficking of synaptic vesicles. Curr. Biol. 15: 684– 689 10.1016/j.cub.2005.02.061 15823543 · DOI
- Nieratschker V. Schubert A. Jauch M. Bock N. Bucher D. Dippacher S. Krohne G. Asan E. Buchner S. Buchner E. 2009 Bruchpilot in ribbon-like axonal agglomerates, behavioral defects, and early death in SRPK79D kinase mutants of Drosophila. PLoS Genet. 5: e1000700 10.1371/journal.pgen.1000700 19851455 PMC2759580 · DOI
- Owald D. Sigrist S.J. 2009 Assembling the presynaptic active zone. Curr. Opin. Neurobiol. 19: 311– 318 10.1016/j.conb.2009.03.003 19395253 · DOI
- Pack-Chung E. Kurshan P.T. Dickman D.K. Schwarz T.L. 2007 A Drosophila kinesin required for synaptic bouton formation and synaptic vesicle transport. Nat. Neurosci. 10: 980– 989 10.1038/nn1936 17643120 · DOI
- Parks A.L. Cook K.R. Belvin M. Dompe N.A. Fawcett R. Huppert K. Tan L.R. Winter C.G. Bogart K.P. Deal J.E. 2004 Systematic generation of high-resolution deletion coverage of the Drosophila melanogaster genome. Nat. Genet. 36: 288– 292 10.1038/ng1312 14981519 · DOI
- Patel M.R. Shen K. 2009 RSY-1 is a local inhibitor of presynaptic assembly in C. elegans. Science. 323: 1500– 1503 10.1126/science.1169025 19286562 PMC3087376 · DOI
- Patel M.R. Lehrman E.K. Poon V.Y. Crump J.G. Zhen M. Bargmann C.I. Shen K. 2006 Hierarchical assembly of presynaptic components in defined C. elegans synapses. Nat. Neurosci. 9: 1488– 1498 10.1038/nn1806 17115039 PMC3917495 · DOI · Paper page
- Petersen S.A. Fetter R.D. Noordermeer J.N. Goodman C.S. DiAntonio A. 1997 Genetic analysis of glutamate receptors in Drosophila reveals a retrograde signal regulating presynaptic transmitter release. Neuron. 19: 1237– 1248 10.1016/S0896-6273(00)80415-8 9427247 · DOI
- Pilling A.D. Horiuchi D. Lively C.M. Saxton W.M. 2006 Kinesin-1 and Dynein are the primary motors for fast transport of mitochondria in Drosophila motor axons. Mol. Biol. Cell. 17: 2057– 2068 10.1091/mbc.E05-06-0526 16467387 PMC1415296 · DOI
- Qin G. Schwarz T. Kittel R.J. Schmid A. Rasse T.M. Kappei D. Ponimaskin E. Heckmann M. Sigrist S.J. 2005 Four different subunits are essential for expressing the synaptic glutamate receptor at neuromuscular junctions of Drosophila. J. Neurosci. 25: 3209– 3218 10.1523/JNEUROSCI.4194-04.2005 15788778 PMC6725071 · DOI
- Raghu S.V. Joesch M. Sigrist S.J. Borst A. Reiff D.F. 2009 Synaptic organization of lobula plate tangential cells in Drosophila: Dalpha7 cholinergic receptors. J. Neurogenet. 23: 200– 209 10.1080/01677060802471684 19306209 · DOI
- Rasse T.M. Fouquet W. Schmid A. Kittel R.J. Mertel S. Sigrist C.B. Schmidt M. Guzman A. Merino C. Qin G. 2005 Glutamate receptor dynamics organizing synapse formation in vivo. Nat. Neurosci. 8: 898– 905 16136672
- Rostaing P. Real E. Siksou L. Lechaire J.P. Boudier T. Boeckers T.M. Gertler F. Gundelfinger E.D. Triller A. Marty S. 2006 Analysis of synaptic ultrastructure without fixative using high-pressure freezing and tomography. Eur. J. Neurosci. 24: 3463– 3474 10.1111/j.1460-9568.2006.05234.x 17229095 · DOI
- Schmid A. Qin G. Wichmann C. Kittel R.J. Mertel S. Fouquet W. Schmidt M. Heckmann M. Sigrist S.J. 2006 Non-NMDA-type glutamate receptors are essential for maturation but not for initial assembly of synapses at Drosophila neuromuscular junctions. J. Neurosci. 26: 11267– 11277 10.1523/JNEUROSCI.2722-06.2006 17079654 PMC6674544 · DOI
- Schmid A. Hallermann S. Kittel R.J. Khorramshahi O. Frölich A.M. Quentin C. Rasse T.M. Mertel S. Heckmann M. Sigrist S.J. 2008 Activity-dependent site-specific changes of glutamate receptor composition in vivo. Nat. Neurosci. 11: 659– 666 10.1038/nn.2122 18469810 · DOI
- Schoch S. Gundelfinger E.D. 2006 Molecular organization of the presynaptic active zone. Cell Tissue Res. 326: 379– 391 10.1007/s00441-006-0244-y 16865347 · DOI
- Shevchenko A. Wilm M. Vorm O. Mann M. 1996 Mass spectrometric sequencing of proteins silver-stained polyacrylamide gels. Anal. Chem. 68: 850– 858 10.1021/ac950914h 8779443 · DOI
- Shin H. Wyszynski M. Huh K.H. Valtschanoff J.G. Lee J.R. Ko J. Streuli M. Weinberg R.J. Sheng M. Kim E. 2003 Association of the kinesin motor KIF1A with the multimodular protein liprin-alpha. J. Biol. Chem. 278: 11393– 11401 10.1074/jbc.M211874200 12522103 · DOI
- Sigrist S.J. Reiff D.F. Thiel P.R. Steinert J.R. Schuster C.M. 2003 Experience-dependent strengthening of Drosophila neuromuscular junctions. J. Neurosci. 23: 6546– 6556 12878696 PMC6740647
- Siksou L. Rostaing P. Lechaire J.P. Boudier T. Ohtsuka T. Fejtová A. Kao H.T. Greengard P. Gundelfinger E.D. Triller A. Marty S. 2007 Three-dimensional architecture of presynaptic terminal cytomatrix. J. Neurosci. 27: 6868– 6877 10.1523/JNEUROSCI.1773-07.2007 17596435 PMC6672225 · DOI
- van Roessel P. Elliott D.A. Robinson I.M. Prokop A. Brand A.H. 2004 Independent regulation of synaptic size and activity by the anaphase-promoting complex. Cell. 119: 707– 718 10.1016/j.cell.2004.11.028 15550251 · DOI
- Wagh D.A. Rasse T.M. Asan E. Hofbauer A. Schwenkert I. Dürrbeck H. Buchner S. Dabauvalle M.C. Schmidt M. Qin G. 2006 Bruchpilot, a protein with homology to ELKS/CAST, is required for structural integrity and function of synaptic active zones in Drosophila. Neuron. 49: 833– 844 10.1016/j.neuron.2006.02.008 16543132 · DOI · Paper page
- Wagner O.I. Esposito A. Köhler B. Chen C.W. Shen C.P. Wu G.H. Butkevich E. Mandalapu S. Wenzel D. Wouters F.S. Klopfenstein D.R. 2009 Synaptic scaffolding protein SYD-2 clusters and activates kinesin-3 UNC-104 in C. elegans. Proc. Natl. Acad. Sci. USA. 106: 19605– 19610 10.1073/pnas.0902949106 19880746 PMC2780759 · DOI
- Wairkar Y.P. Toda H. Mochizuki H. Furukubo-Tokunaga K. Tomoda T. Diantonio A. 2009 Unc-51 controls active zone density and protein composition by downregulating ERK signaling. J. Neurosci. 29: 517– 528 10.1523/JNEUROSCI.3848-08.2009 19144852 PMC2741695 · DOI · Paper page
- Wu J.S. Luo L. 2006 A protocol for dissecting Drosophila melanogaster brains for live imaging or immunostaining. Nat. Protoc. 1: 2110– 2115 10.1038/nprot.2006.336 17487202 · DOI
- Wyszynski M. Kim E. Dunah A.W. Passafaro M. Valtschanoff J.G. Serra-Pagès C. Streuli M. Weinberg R.J. Sheng M. 2002 Interaction between GRIP and liprin-alpha/SYD2 is required for AMPA receptor targeting. Neuron. 34: 39– 52 10.1016/S0896-6273(02)00640-2 11931740 · DOI
Cited by
Sorted by citations
Südhof, T. C. (2012) · Neuron · doi:10.1016/j.neuron.2012.06.012 · Cited by 1,062 · see citing works
Tsao, C.-H., Chen, C.-C., Lin, C.-H., Yang, H.-Y., & Lin, S. (2018) · eLife · doi:10.7554/elife.35264 · Cited by 214 · see citing works
Endonuclease G mediates α‐synuclein cytotoxicity during Parkinson's disease
Büttner, S., Habernig, L., Broeskamp, F., Ruli, D., Vögtle, F. N., Vlachos, M., Macchi, F., Küttner, V., Carmona‐Gutierrez, D., Eisenberg, T., et al. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.228 · Cited by 87 · see citing works
Self-citationTaru, H., & Jin, Y. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.0002-11.2011 · Cited by 49 · see citing works
Principles of synaptogenesis: Insights from Caenorhabditis elegans
Frankel, E. B., & Kurshan, P. T. (2025) · Current Opinion in Neurobiology · doi:10.1016/j.conb.2025.103056 · Cited by 7 · see citing works
- Authors
- Owald, D., Fouquet, W., Schmidt, M., Wichmann, C., Mertel, S., Depner, H., Christiansen, F., Zube, C., Quentin, C., Körner, J., Urlaub, H., Mechtler, K., & Sigrist, S. J.
- Affiliations
- University of Würzburg (DE)
- European Neuroscience Institute Göttingen (DE)
- Freie Universität Berlin (DE)
- Max Planck Institute for Biophysical Chemistry (DE)
- Research Institute of Molecular Pathology (AT)
- Corresponding author
- Sigrist, Stephan J.
- ORCID
- Venue
- Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2010-02-22
- Volume
- 188
- Issue
- 4
- Pages
- 565-579
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2828917
- OpenAlex
- W1969837542
- Cited by
- 191
- References
- 3
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 10 · 2023: 12 · 2022: 8 · 2021: 8 · 2020: 11 · 2019: 12 · 2018: 17 · 2017: 13 · 2016: 8 · 2015: 20 · 2014: 13 · 2013: 14 · 2012: 13
- FWCI
- 5.18
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- 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 › Neuroscience › Cellular and Molecular Neuroscience › Neurobiology and Insect Physiology Research
- Keywords
- Bruchpilot, elk, postsynaptic density, neuromuscular junction, synaptic vesicle release, trans-synaptic signaling, Drosophila
- MeSH terms
- Animals, Drosophila melanogaster, Embryo, Nonmammalian, Locomotion, Longevity, Mutation, Neuromuscular Junction, Phenotype, Phosphoproteins, Protein Binding, Sequence Homology, Amino Acid, Receptors, Glutamate, Presynaptic Terminals, GTPase-Activating Proteins, Protein Transport, Drosophila Proteins, Proteomics, Intracellular Signaling Peptides and Proteins, Synaptic Potentials
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
