Mutations in Drosophila sec15 Reveal a Function in Neuronal Targeting for a Subset of Exocyst Components
Open accessAbstract
The exocyst is a complex of proteins originally identified in yeast that has been implicated in polarized secretion. Components of the exocyst have been implicated in neurite outgrowth, cell polarity, and cell viability. We have isolated an exocyst component, sec15, in a screen for genes required for synaptic specificity. Loss of sec15 causes a targeting defect of photoreceptors that coincides with mislocalization of specific cell adhesion and signaling molecules. Additionally, sec15 mutant neurons fail to localize other exocyst members like Sec5 and Sec8, but not Sec6, to neuronal terminals. However, loss of sec15 does not cause cell lethality in contrast to loss of sec5 or sec6. Our data suggest a role of Sec15 in an exocyst-like subcomplex for the targeting and subcellular distribution of specific proteins. The data also show that functions of other exocyst components persist in the absence of sec15, suggesting that different exocyst components have separable functions.
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?
The distribution of the exocyst within a cell can be highly dynamic, consistent with its role in directing membrane fusion to specific domains.
“The distribution of the exocyst within a cell can be highly dynamic, consistent with its role in directing membrane fusion to specific domains (Boyd et al, 2004;Beronja et al, 2005;Mehta et al, 2005;Zhang et al, 2008;Murthy et al, 2010).”
From Ral mediates activity‐dependent growth of postsynaptic membranes via recruitment of the exocyst (2013) · cites this paper as Mehta et al, 2005
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
No references could be resolved yet.
Research works printed but not linked: 42
- [1]1. Andrews, H.K. ∙ Zhang, Y.Q. ∙ Trotta, N. ... Drosophila Sec10 is required for hormone secretion but not general exocytosis or neurotransmission Traffic. 2002; 3:906-921 Crossref Scopus (43) PubMed Google Scholar
- [2]2. Ang, A.L. ∙ Taguchi, T. ∙ Francis, S. ... Recycling endosomes can serve as intermediates during transport from the Golgi to the plasma membrane of MDCK cells J. Cell Biol. 2004; 167:531-543 Crossref Scopus (352) PubMed Google Scholar
- [3]3. Barton, W.A. ∙ Liu, B.P. ∙ Tzvetkova, D. ... Structure and axon outgrowth inhibitor binding of the Nogo-66 receptor and related proteins EMBO J. 2003; 22:3291-3302 Crossref Scopus (198) PubMed Google Scholar
- [4]4. Bennett, M.K. ∙ Scheller, R.H. The molecular machinery for secretion is conserved from yeast to neurons Proc. Natl. Acad. Sci. USA. 1993; 90:2559-2563 Crossref Scopus (557) PubMed Google Scholar
- [5]5. Benzer, S. Behavioral mutants of Drosophila isolated by countercurrent distribution Proc. Natl. Acad. Sci. USA. 1967; 58:1112-1119 Crossref PubMed Google Scholar
- [6]6. Boyd, C. ∙ Hughes, T. ∙ Pypaert, M. ... Vesicles carry most exocyst subunits to exocytic sites marked by the remaining two subunits, Sec3p and Exo70p J. Cell Biol. 2004; 167:889-901 Crossref Scopus (247) PubMed Google Scholar
- [7]7. Burg, M. ∙ Sarthy, P. ∙ Koliantz, G. ... Genetic and molecular identification of a Drosophila histidine decarboxylase gene required in photoreceptor transmitter synthesis EMBO J. 1993; 12:911-919 Crossref Scopus (104) PubMed Google Scholar
- [8]8. Clandinin, T.R. ∙ Zipursky, S.L. Afferent growth cone interactions control synaptic specificity in the Drosophila visual system Neuron. 2000; 28:427-436 Full Text Full Text (PDF) Scopus (85) PubMed Google Scholar
- [9]9. Clandinin, T.R. ∙ Zipursky, S.L. Making connections in the fly visual system Neuron. 2002; 35:827-841 Full Text Full Text (PDF) Scopus (144) PubMed Google Scholar
- [10]10. Clandinin, T.R. ∙ Lee, C.-H. ∙ Herman, T. ... Drosophila LAR Regulates R1–R6 and R7 Target Specificity in the Visual System Neuron. 2001; 32:237-248 Full Text Full Text (PDF) Scopus (131) PubMed Google Scholar
- [11]11. Duden, R. ER-to-Golgi transport: COP I and COP II function (Review) Mol. Membr. Biol. 2003; 20:197-207 Crossref Scopus (136) PubMed Google Scholar
- [12]12. Elul, T.M. ∙ Kimes, N.E. ∙ Kohwi, M. ... N- and C-terminal domains of beta-catenin, respectively, are required to initiate and shape axon arbors of retinal ganglion cells in vivo J. Neurosci. 2003; 23:6567-6575 Crossref PubMed Google Scholar
- [13]13. Finger, F.P. ∙ Novick, P. Spatial regulation of exocytosis: lessons from yeast J. Cell Biol. 1998; 142:609-612 Crossref Scopus (126) PubMed Google Scholar
- [14]14. Fischbach, K. ∙ Dittrich, A. The optic lobe of Drosophila melanogaster. I. A golgi analysis of wild-type structure Cell Tissue Res. 1989; 258:441-475 Crossref Scopus (597) Google Scholar
- [15]15. Friedrich, G.A. ∙ Hildebrand, J.D. ∙ Soriano, P. The secretory protein Sec8 is required for paraxial mesoderm formation in the mouse Dev. Biol. 1997; 192:364-374 Crossref Scopus (63) PubMed Google Scholar
- [16]16. Frohlich, A. ∙ Meinertzhagen, I.A. Quantitative features of synapse formation in the fly’s visual system. I. The presynaptic photoreceptor terminal J. Neurosci. 1983; 3:2336-2349 Crossref PubMed Google Scholar
- [17]17. Fujita, S. ∙ Zipursky, S. ∙ Benzer, S. ... Monoclonal antibodies against the Drosophila nervous system Proc. Natl. Acad. Sci. USA. 1982; 79:7929-7933 Crossref Scopus (485) PubMed Google Scholar
- [18]18. Grindstaff, K.K. ∙ Yeaman, C. ∙ Anandasabapathy, N. ... Sec6/8 complex is recruited to cell-cell contacts and specifies transport vesicle delivery to the basal-lateral membrane in epithelial cells Cell. 1998; 93:731-740 Full Text Full Text (PDF) Scopus (454) PubMed Google Scholar
- [19]19. Guo, W. ∙ Roth, D. ∙ Walch-Solimena, C. ... The exocyst is an effector for Sec4p, targeting secretory vesicles to sites of exocytosis EMBO J. 1999; 18:1071-1080 Crossref Scopus (513) PubMed Google Scholar
- [20]20. Guo, W. ∙ Sacher, M. ∙ Barrowman, J. ... Protein complexes in transport vesicle targeting Trends Cell Biol. 2000; 10:251-255 Full Text Full Text (PDF) Scopus (178) PubMed Google Scholar
- [21]21. Hazuka, C.D. ∙ Foletti, D.L. ∙ Hsu, S.-C. ... The sec6/8 complex is located at neurite outgrowth and axonal synapse-assembly domains J. Neurosci. 1999; 19:1324-1334 Crossref PubMed Google Scholar
- [22]22. Hiesinger, P.R. ∙ Reiter, C. ∙ Schau, H. ... Neuropil pattern formation and regulation of cell adhesion molecules in Drosophila optic lobe development depend on synaptobrevin J. Neurosci. 1999; 19:7548-7556 Crossref PubMed Google Scholar
- [23]23. Hiesinger, P.R. ∙ Scholz, M. ∙ Meinertzhagen, I.A. ... Visualization of synaptic markers in the optic neuropils of Drosophila using a new constrained deconvolution method J. Comp. Neurol. 2001; 429:277-288 Crossref Scopus (30) PubMed Google Scholar
- [24]24. Hsu, S.C. ∙ Ting, A.E. ∙ Hazuka, C.D. ... The mammalian brain rsec6/8 complex Neuron. 1996; 17:1209-1219 Full Text Full Text (PDF) Scopus (231) PubMed Google Scholar
- [25]25. Hsu, S.-C. ∙ Hazuka, C.D. ∙ Foletti, D.L. ... Targeting vesicles to specific sites on the plasma membrane: the role of the sec6/8 complex Trends Cell Biol. 1999; 9:150-153 Full Text Full Text (PDF) Scopus (132) PubMed Google Scholar
- [26]26. Hsu, S.C. ∙ TerBush, D. ∙ Abraham, M. ... The exocyst complex in polarized exocytosis Int. Rev. Cytol. 2004; 233:243-265 Crossref Scopus (212) PubMed Google Scholar
- [27]27. Inoue, M. ∙ Chang, L. ∙ Hwang, J. ... The exocyst complex is required for targeting of Glut4 to the plasma membrane by insulin Nature. 2003; 422:629-633 Crossref Scopus (288) PubMed Google Scholar
- [28]28. Izaddoost, S. ∙ Nam, S.C. ∙ Bhat, M.A. ... Drosophila Crumbs is a positional cue in photoreceptor adherens junctions and rhabdomeres Nature. 2002; 416:178-183 Crossref Scopus (231) PubMed Google Scholar
- [29]29. Kaufmann, N. ∙ DeProto, J. ∙ Ranjan, R. ... Drosophila liprin-alpha and the receptor phosphatase Dlar control synapse morphogenesis Neuron. 2002; 34:27-38 Full Text Full Text (PDF) Scopus (249) PubMed Google Scholar
- [30]30. Kee, Y. ∙ Yoo, J.-S. ∙ Hazuka, C.D. ... Subunit structure of the mammalian exocyst complex Proc. Natl. Acad. Sci. USA. 1997; 94:14438-14443 Crossref Scopus (151) PubMed Google Scholar
- [31]31. Kirschfeld, K. Exp. Brain Res. 1967; 3:248-270 Crossref Scopus (234) PubMed Google Scholar
- [32]32. Lee, T. ∙ Luo, L. Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis Neuron. 1999; 22:451-461 Full Text Full Text (PDF) Scopus (2074) PubMed Google Scholar
- [33]33. Lee, T. ∙ Luo, L. Mosaic analysis with a repressible cell marker (MARCM) for Drosophila neural development Trends Neurosci. 2001; 24:251-254 Full Text Full Text (PDF) Scopus (741) PubMed Google Scholar
- [34]34. Lee, C.H. ∙ Herman, T. ∙ Clandinin, T.R. ... N-cadherin regulates target specificity in the Drosophila visual system Neuron. 2001; 30:437-450 Full Text Full Text (PDF) Scopus (226) PubMed Google Scholar
- [35]35. Lee, R.C. ∙ Clandinin, T.R. ∙ Lee, C.-H. ... The protocadherin Flamingo is required for axon target selection in the Drosophila visual system Nat. Neurosci. 2003; 6:557-563 Crossref Scopus (138) PubMed Google Scholar
- [36]36. Maurel-Zaffran, C. ∙ Suzuki, T. ∙ Gahmon, G. ... Cell-autonomous and -nonautonomous functions of LAR in R7 photoreceptor axon targeting Neuron. 2001; 32:225-235 Full Text Full Text (PDF) Scopus (113) PubMed Google Scholar
- [37]37. Meinertzhagen, I.A. ∙ Hanson, T.E. The development of the optic lobe Bate, M. ∙ Martinez-Arias, A. (Editors) The Development of Drosophila Melanogaster Cold Spring Harbor Press, Cold Spring Harbor, NY, 1993; 1363-1491 Google Scholar
- [38]38. Murthy, M. ∙ Schwarz, T.L. The exocyst component Sec5 is required for membrane traffic and polarity in the Drosophila ovary Development. 2004; 131:377-388 Crossref Scopus (52) PubMed Google Scholar
- [39]39. Murthy, M. ∙ Garza, D. ∙ Scheller, R.H. ... Mutations in the exocyst component Sec5 disrupt neuronal membrane traffic, but neurotransmitter release persists Neuron. 2003; 37:433-447 Full Text Full Text (PDF) Scopus (170) PubMed Google Scholar
- [40]40. Nelson, W.J. Adaptation of core mechanisms to generate cell polarity Nature. 2003; 422:766-774 Crossref Scopus (593) PubMed Google Scholar
- [41]41. Newsome, T.P. ∙ Asling, B. ∙ Dickson, B.J. Analysis of Drosophila photoreceptor axon guidance in eye-specific mosaics Development. 2000; 127:851-860 Crossref PubMed Google Scholar
- [42]42. Novick, P. ∙ Field, C. ∙ Schekman, R. Identification of 23 complementation groups required for post-translational events in the yeast secretory pathway Cell. 1980; 21:205-215
Cited by
Sorted by citations
Glial Lipid Droplets and ROS Induced by Mitochondrial Defects Promote Neurodegeneration
Liu, L., Zhang, K., Sandoval, H., Yamamoto, S., Jaiswal, M., Sanz, E., Li, Z., Hui, J., Graham, B. H., Quintana, A., et al. (2015) · Cell · doi:10.1016/j.cell.2014.12.019 · Cited by 876 · see citing works
Self-citationRal mediates activity‐dependent growth of postsynaptic membranes via recruitment of the exocyst
Teodoro, R. O., Pekkurnaz, G., Nasser, A., Higashi‐Kovtun, M. E., Balakireva, M., McLachlan, I. G., Camonis, J., & Schwarz, T. L. (2013) · The EMBO Journal · doi:10.1038/emboj.2013.147 · Cited by 61 · see citing works
- Authors
- Mehta, S. Q., Hiesinger, P. R., Beronja, S., Zhai, R. G., Schulze, K. L., Verstreken, P., Cao, Y., Zhou, Y., Tepass, U., Crair, M. C., & Bellen, H. J.
- Affiliations
- Baylor College of Medicine (US)
- Howard Hughes Medical Institute (US)
- University of Toronto (CA)
- Corresponding author
- Bellen, Hugo J.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2005-04
- Volume
- 46
- Issue
- 2
- Pages
- 219-232
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2107396888
- Cited by
- 136
- References
- 0
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 5 · 2022: 1 · 2021: 4 · 2020: 5 · 2019: 5 · 2018: 3 · 2017: 3 · 2016: 7 · 2015: 8 · 2014: 7 · 2013: 8 · 2012: 10
- FWCI
- 4.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 3029 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Lirias (submittedVersion)
- Funders
- National Institute of Mental Health (MH62639, R01MH062639)
- National Eye Institute (EY-07001, R01EY015788)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Keywords
- exocyst, Sec15, Sec5, Sec8, Sec6, synaptic specificity, neuronal targeting, photoreceptors, polarized secretion, adhesion molecules, signaling molecules, subcellular localization, Drosophila
- MeSH terms
- Amino Acid Sequence, Animals, Drosophila, Exocytosis, Humans, Immunohistochemistry, Membrane Proteins, Molecular Sequence Data, Mutation, Neurons, Synapses, Blotting, Western, Polymerase Chain Reaction, Sequence Homology, Amino Acid, Protein Transport, Microscopy, Electron, Transmission
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