Mutations in the Exocyst Component Sec5 Disrupt Neuronal Membrane Traffic, but Neurotransmitter Release Persists
Open accessAbstract
The exocyst (Sec6/8) complex is necessary for secretion in yeast and has been postulated to establish polarity by directing vesicle fusion to specific sites along the plasma membrane. The complex may also function in the nervous system, but its precise role is unknown. We have investigated exocyst function in Drosophila with mutations in one member of the complex, sec5. Null alleles die as growth-arrested larvae, whose neuromuscular junctions fail to expand. In culture, neurite outgrowth fails in sec5 mutants once maternal Sec5 is exhausted. Using a trafficking assay, we found impairments in the membrane addition of newly synthesized proteins. In contrast, synaptic vesicle fusion was not impaired. Thus, Sec5 differentiates between two forms of vesicle trafficking: trafficking for cell growth and membrane protein insertion depend on sec5, whereas transmitter secretion does not. In this regard, sec5 differs from the homologs of other yeast exocytosis genes that are required for both neuronal trafficking pathways.
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The exocyst is required for neurite outgrowth and the addition of neuronal membrane proteins, including the insertion of glutamate receptors, and the maturation of photoreceptors.
“It is required for neurite outgrowth and the addition of neuronal membrane proteins, including the insertion of glutamate receptors, and the maturation of photoreceptors (Brymora et al, 2001;Vega and Hsu, 2001;Murthy et al, 2003;Sans et al, 2003;Beronja et al, 2005;Liebl et al, 2005;Mehta et al, 2005;Gerges et al, 2006).”
From Ral mediates activity‐dependent growth of postsynaptic membranes via recruitment of the exocyst (2013) · cites this paper as Murthy et al, 2003
The Results (page unavailable) conclude that Sec5 is required for neurite outgrowth and show that loss of Sec5 impairs insertion of the mCD8 membrane-protein reporter into neuronal surfaces. Our copy does not establish that this paper supports glutamate-receptor insertion or photoreceptor maturation, the other examples in the multiply cited sentence. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe exocyst is not required for the exocytosis of synaptic vesicles.
“although not required for the exocytosis of synaptic vesicles (Murthy et al, 2003)”
From Ral mediates activity‐dependent growth of postsynaptic membranes via recruitment of the exocyst (2013) · cites this paper as Murthy et al, 2003
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Research works printed but not linked: 7
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Ral 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
Self-citation
- Authors
- Murthy, M., Garza, D., Scheller, R. H., & Schwarz, T. L.
- Affiliations
- Howard Hughes Medical Institute (US)
- Florida State University (US)
- Harvard University (US)
- Corresponding author
- Schwarz, Thomas L.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2003-02
- Volume
- 37
- Issue
- 3
- Pages
- 433-447
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2023140943
- Cited by
- 202
- References
- 0
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 5 · 2023: 7 · 2022: 1 · 2021: 5 · 2020: 4 · 2019: 6 · 2018: 7 · 2017: 7 · 2016: 8 · 2015: 10 · 2014: 9 · 2013: 8 · 2012: 5
- FWCI
- 6.91
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (P50MH048108, MH 48108, 5T32 MH20016-04, T32MH020016)
- National Institute of Neurological Disorders and Stroke (R01NS041062, NS-41062)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Extracellular vesicles in disease
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- exocyst, Sec5, neurotransmitter release, synaptic vesicle fusion, neuromuscular junction, neurite outgrowth, membrane protein insertion, Drosophila, exocytosis, cell polarity
- MeSH terms
- Animals, Cell Membrane, Chromosome Mapping, Drosophila, Exocytosis, Synaptic Transmission, Neuromuscular Junction, Neurons, Synaptic Vesicles, Mutagenesis, Neurites, Neurotransmitter Agents, Protein Transport, Saccharomyces cerevisiae Proteins
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