Expressing acetylcholine receptors after innervation suppresses spontaneous vesicle release and causes muscle fatigue
Abstract The formation and function of synapses are tightly orchestrated by the precise timing of expression of specific molecules during development. In this study, we determined how manipulating the timing of expression of postsynaptic acetylcholine receptors (AChRs) impacts presynaptic release by...
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| Format: | Article |
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Nature Portfolio
2017-05-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-017-01900-3 |
| _version_ | 1818839872026181632 |
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| author | Meghan Mott Victor M. Luna Jee-Young Park Gerald B. Downes Kimberly Epley Fumihito Ono |
| author_facet | Meghan Mott Victor M. Luna Jee-Young Park Gerald B. Downes Kimberly Epley Fumihito Ono |
| author_sort | Meghan Mott |
| collection | DOAJ |
| description | Abstract The formation and function of synapses are tightly orchestrated by the precise timing of expression of specific molecules during development. In this study, we determined how manipulating the timing of expression of postsynaptic acetylcholine receptors (AChRs) impacts presynaptic release by establishing a genetically engineered zebrafish line in which we can freely control the timing of AChR expression in an AChR-less fish background. With the delayed induction of AChR expression after an extensive period of AChR-less development, paralyzed fish displayed a remarkable level of recovery, exhibiting a robust escape response following developmental delay. Despite their apparent behavioral rescue, synapse formation in these fish was significantly altered as a result of delayed AChR expression. Motor neuron innervation determined the sites for AChR clustering, a complete reversal of normal neuromuscular junction (NMJ) development where AChR clustering precedes innervation. Most importantly, among the three modes of presynaptic vesicle release, only the spontaneous release machinery was strongly suppressed in these fish, while evoked vesicle release remained relatively unaffected. Such a specific presynaptic change, which may constitute a part of the compensatory mechanism in response to the absence of postsynaptic AChRs, may underlie symptoms of neuromuscular diseases characterized by reduced AChRs, such as myasthenia gravis. |
| first_indexed | 2024-12-19T04:01:11Z |
| format | Article |
| id | doaj.art-5ea36b414a424755a8be621a6f3de34a |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-19T04:01:11Z |
| publishDate | 2017-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-5ea36b414a424755a8be621a6f3de34a2022-12-21T20:36:41ZengNature PortfolioScientific Reports2045-23222017-05-01711810.1038/s41598-017-01900-3Expressing acetylcholine receptors after innervation suppresses spontaneous vesicle release and causes muscle fatigueMeghan Mott0Victor M. Luna1Jee-Young Park2Gerald B. Downes3Kimberly Epley4Fumihito Ono5Section on Model Synaptic Systems, Laboratory of Molecular Physiology, NIAAA, NIHSection on Model Synaptic Systems, Laboratory of Molecular Physiology, NIAAA, NIHSection on Model Synaptic Systems, Laboratory of Molecular Physiology, NIAAA, NIHBiology Department, University of Massachusetts Amherst, AmherstWhitney laboratory for Marine Bioscience, University of Florida, St. AugustineSection on Model Synaptic Systems, Laboratory of Molecular Physiology, NIAAA, NIHAbstract The formation and function of synapses are tightly orchestrated by the precise timing of expression of specific molecules during development. In this study, we determined how manipulating the timing of expression of postsynaptic acetylcholine receptors (AChRs) impacts presynaptic release by establishing a genetically engineered zebrafish line in which we can freely control the timing of AChR expression in an AChR-less fish background. With the delayed induction of AChR expression after an extensive period of AChR-less development, paralyzed fish displayed a remarkable level of recovery, exhibiting a robust escape response following developmental delay. Despite their apparent behavioral rescue, synapse formation in these fish was significantly altered as a result of delayed AChR expression. Motor neuron innervation determined the sites for AChR clustering, a complete reversal of normal neuromuscular junction (NMJ) development where AChR clustering precedes innervation. Most importantly, among the three modes of presynaptic vesicle release, only the spontaneous release machinery was strongly suppressed in these fish, while evoked vesicle release remained relatively unaffected. Such a specific presynaptic change, which may constitute a part of the compensatory mechanism in response to the absence of postsynaptic AChRs, may underlie symptoms of neuromuscular diseases characterized by reduced AChRs, such as myasthenia gravis.https://doi.org/10.1038/s41598-017-01900-3 |
| spellingShingle | Meghan Mott Victor M. Luna Jee-Young Park Gerald B. Downes Kimberly Epley Fumihito Ono Expressing acetylcholine receptors after innervation suppresses spontaneous vesicle release and causes muscle fatigue Scientific Reports |
| title | Expressing acetylcholine receptors after innervation suppresses spontaneous vesicle release and causes muscle fatigue |
| title_full | Expressing acetylcholine receptors after innervation suppresses spontaneous vesicle release and causes muscle fatigue |
| title_fullStr | Expressing acetylcholine receptors after innervation suppresses spontaneous vesicle release and causes muscle fatigue |
| title_full_unstemmed | Expressing acetylcholine receptors after innervation suppresses spontaneous vesicle release and causes muscle fatigue |
| title_short | Expressing acetylcholine receptors after innervation suppresses spontaneous vesicle release and causes muscle fatigue |
| title_sort | expressing acetylcholine receptors after innervation suppresses spontaneous vesicle release and causes muscle fatigue |
| url | https://doi.org/10.1038/s41598-017-01900-3 |
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