Synaptic vesicle characterization of iPSC-derived dopaminergic neurons provides insight into distinct secretory vesicle pools
Abstract The dysfunction of dopaminergic (DA) neurons is central to Parkinson’s disease. Distinct synaptic vesicle (SV) populations, differing in neurotransmitter content (dopamine vs. glutamate), may vary due to differences in trafficking and exocytosis. However, the structural organization of thes...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | npj Parkinson's Disease |
| Online Access: | https://doi.org/10.1038/s41531-024-00862-4 |
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| author | Kenshiro Fujise Jaya Mishra Martin Shaun Rosenfeld Nisha Mohd Rafiq |
| author_facet | Kenshiro Fujise Jaya Mishra Martin Shaun Rosenfeld Nisha Mohd Rafiq |
| author_sort | Kenshiro Fujise |
| collection | DOAJ |
| description | Abstract The dysfunction of dopaminergic (DA) neurons is central to Parkinson’s disease. Distinct synaptic vesicle (SV) populations, differing in neurotransmitter content (dopamine vs. glutamate), may vary due to differences in trafficking and exocytosis. However, the structural organization of these vesicles remains unclear. In this study, we examined axonal varicosities in human iPSC-derived DA and glutamatergic neurons (i3Neurons). i3Neurons primarily contained small, clear SVs (40–50 nm), whereas DA neurons contained larger, pleiomorphic vesicles including dense core and empty vesicles, in addition to the classical SVs. VMAT2-positive vesicles in DA neurons, which load dopamine, were spatially segregated from VGLUT1/2-positive vesicles in an SV-like reconstitution system. These vesicles also colocalized with SV markers (e.g., VAMP2, SV2C), and can be clustered by synapsin. Moreover, DA axonal terminals in mouse striata showed similar vesicle pool diversity. These findings reveal structural differences in DA neurons’ vesicles, highlighting iPSC-derived neurons as effective models for studying presynaptic structures. |
| format | Article |
| id | doaj-art-eff77f6ea20b452886bfccb08fa6750a |
| institution | Kabale University |
| issn | 2373-8057 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Parkinson's Disease |
| spelling | doaj-art-eff77f6ea20b452886bfccb08fa6750a2025-01-12T12:12:38ZengNature Portfolionpj Parkinson's Disease2373-80572025-01-0111111610.1038/s41531-024-00862-4Synaptic vesicle characterization of iPSC-derived dopaminergic neurons provides insight into distinct secretory vesicle poolsKenshiro Fujise0Jaya Mishra1Martin Shaun Rosenfeld2Nisha Mohd Rafiq3Department of Neuroscience, Yale University School of MedicineInterfaculty Institute of Biochemistry, University of TübingenDepartment of Neuroscience, Yale University School of MedicineInterfaculty Institute of Biochemistry, University of TübingenAbstract The dysfunction of dopaminergic (DA) neurons is central to Parkinson’s disease. Distinct synaptic vesicle (SV) populations, differing in neurotransmitter content (dopamine vs. glutamate), may vary due to differences in trafficking and exocytosis. However, the structural organization of these vesicles remains unclear. In this study, we examined axonal varicosities in human iPSC-derived DA and glutamatergic neurons (i3Neurons). i3Neurons primarily contained small, clear SVs (40–50 nm), whereas DA neurons contained larger, pleiomorphic vesicles including dense core and empty vesicles, in addition to the classical SVs. VMAT2-positive vesicles in DA neurons, which load dopamine, were spatially segregated from VGLUT1/2-positive vesicles in an SV-like reconstitution system. These vesicles also colocalized with SV markers (e.g., VAMP2, SV2C), and can be clustered by synapsin. Moreover, DA axonal terminals in mouse striata showed similar vesicle pool diversity. These findings reveal structural differences in DA neurons’ vesicles, highlighting iPSC-derived neurons as effective models for studying presynaptic structures.https://doi.org/10.1038/s41531-024-00862-4 |
| spellingShingle | Kenshiro Fujise Jaya Mishra Martin Shaun Rosenfeld Nisha Mohd Rafiq Synaptic vesicle characterization of iPSC-derived dopaminergic neurons provides insight into distinct secretory vesicle pools npj Parkinson's Disease |
| title | Synaptic vesicle characterization of iPSC-derived dopaminergic neurons provides insight into distinct secretory vesicle pools |
| title_full | Synaptic vesicle characterization of iPSC-derived dopaminergic neurons provides insight into distinct secretory vesicle pools |
| title_fullStr | Synaptic vesicle characterization of iPSC-derived dopaminergic neurons provides insight into distinct secretory vesicle pools |
| title_full_unstemmed | Synaptic vesicle characterization of iPSC-derived dopaminergic neurons provides insight into distinct secretory vesicle pools |
| title_short | Synaptic vesicle characterization of iPSC-derived dopaminergic neurons provides insight into distinct secretory vesicle pools |
| title_sort | synaptic vesicle characterization of ipsc derived dopaminergic neurons provides insight into distinct secretory vesicle pools |
| url | https://doi.org/10.1038/s41531-024-00862-4 |
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