Delay between Fusion Pore Opening and Peptide Release from Large Dense-Core Vesicles in Neuroendocrine Cells
Open accessAbstract
Peptidergic neurotransmission is slow compared to that mediated by classical neurotransmitters. We have studied exocytotic membrane fusion and cargo release by simultaneous capacitance measurements and confocal imaging of single secretory vesicles in neuroendocrine cells. Depletion of the readily releasable pool (RRP) correlated with exocytosis of 10%-20% of the docked vesicles. Some remaining vesicles became releasable after recovery of RRP. Expansion of the fusion pore, seen as an increase in luminal pH, occurred after approximately 0.3 s, and peptide release was delayed by another 1-10 s. We conclude that (1) RRP refilling involves chemical modification of vesicles already in place, (2) the release of large neuropeptides via the fusion pore is negligible and only proceeds after complete fusion, and (3) sluggish peptidergic transmission reflects the time course of vesicle emptying.
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In the latter studies, most near-membrane granules were immobile, confirming they were functionally as well as morphologically docked.
“In the latter studies, most of these near-membrane granules were immobile, thus confirming they were functionally as well as morphologically docked (49, 288).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [49]
The Results section reports that most vesicles near the plasma membrane were nearly stationary: 69% ± 7% moved less than 0.5 μm in 10 seconds. But the Discussion says the readily releasable pool is only a subset of the docked pool; immobility does not confirm that most near-membrane granules were functionally docked. (LLM, conf=0.88)
Experimental — accuracy not yet measuredGiven that granule mobility is 1.5 μm/s, an increase in the intracellular ATP/ADP ratio increases exocytosis principally by priming of granules that are already situated close to the plasma membrane (within ≈0.5 μm).
“Given that granule mobility is 1.5 μm/s (49, 702), this suggests that an increase in the intracellular ATP/ADP ratio increases exocytosis principally by priming of granules that are already situated close to the plasma membrane (within ≈0.5 μm).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [49]
There is evidence that attachment of a large and bulky protein to proteins involved in exocytosis may influence the kinetics of secretion.
“There is some is evidence that this may influence the kinetics of secretion (49, 445).”
From Pancreatic β-Cell Electrical Activity and Insulin Secretion: Of Mice and Men (2018) · cites this paper as [49]
The Discussion (page unavailable) says that labeling vesicle cargo with IAPP-EGFP did not appear to interfere with vesicle trafficking or, presumably, exocytosis. The paper reports delayed peptide release, but the passages found do not address whether attaching a bulky protein to proteins involved in exocytosis changes secretion kinetics. Searched for bulky protein tags, GFP fusions, and effects on exocytosis kinetics. (LLM, conf=0.72)
Experimental — accuracy not yet measured
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Research works printed but not linked: 8
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Self-citation
- Authors
- Barg, S., Olofsson, C. S., Schriever-Abeln, J., Wendt, A., Gebre-Medhin, S., Renström, E., & Rorsman, P.
- Affiliations
- Lund University (SE)
- Corresponding author
- Barg, Sebastian
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2002-01
- Volume
- 33
- Issue
- 2
- Pages
- 287-299
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2054181228
- Cited by
- 210
- References
- 0
- Citations by year
- 2026: 1 · 2025: 6 · 2024: 3 · 2023: 4 · 2022: 4 · 2021: 3 · 2020: 3 · 2019: 3 · 2018: 6 · 2017: 10 · 2016: 2 · 2015: 8 · 2014: 13 · 2013: 9 · 2012: 7
- FWCI
- 6.58
- 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, 4215 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)
- Lund University Publications (Lund University) (submittedVersion)
- 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
- exocytosis, dense core vesicles, neuroendocrine cells, readily releasable pool, peptide release, neuropeptide release, capacitance measurement
- MeSH terms
- Animals, Cell Line, Electric Stimulation, Exocytosis, Fluorescence, Hydrogen-Ion Concentration, Indicators and Reagents, Kinetics, Luminescent Proteins, Membrane Fusion, Neurosecretory Systems, Peptides, PC12 Cells, Secretory Vesicles, Green Fluorescent Proteins, Rats
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