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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Autores principales:	Meghan Mott, Victor M. Luna, Jee-Young Park, Gerald B. Downes, Kimberly Epley, Fumihito Ono
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/5ea36b414a424755a8be621a6f3de34a
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spelling	oai:doaj.org-article:5ea36b414a424755a8be621a6f3de34a2021-12-02T11:52:31ZExpressing acetylcholine receptors after innervation suppresses spontaneous vesicle release and causes muscle fatigue10.1038/s41598-017-01900-32045-2322https://doaj.org/article/5ea36b414a424755a8be621a6f3de34a2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01900-3https://doaj.org/toc/2045-2322Abstract 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.Meghan MottVictor M. LunaJee-Young ParkGerald B. DownesKimberly EpleyFumihito OnoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q 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
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.
format	article
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
title	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_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_sort	expressing acetylcholine receptors after innervation suppresses spontaneous vesicle release and causes muscle fatigue
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/5ea36b414a424755a8be621a6f3de34a
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Expressing acetylcholine receptors after innervation suppresses spontaneous vesicle release and causes muscle fatigue

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