scholarly journals Septin Polymerization Slows Synaptic Vesicle Recycling in Motor Nerve Endings

Acta Naturae ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 54-62 ◽  
Author(s):  
P. N. Grigoryev ◽  
G. A. Khisamieva ◽  
A. L. Zefirov
Keyword(s):  
Synaptic Vesicle ◽  
High Frequency ◽  
Motor Nerve ◽  
Nerve Endings ◽  
High Frequency Stimulation ◽  
Synaptic Vesicle Recycling ◽  
Vesicle Recycling ◽  
Readily Releasable Pool ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis

Septins are GTP-binding proteins recognized as a component of the cytoskeleton. Despite the fact that septins are highly expressed by neurons and can interact with the proteins that participate in synaptic vesicle exocytosis and endocytosis, the role of septins in synaptic transmission and the synaptic vesicle recycling mechanisms is poorly understood. In this study, neurotransmitter release and synaptic vesicle exocytosis and endocytosis were investigated by microelectrode intracellular recording of end-plate potentials and fluorescent confocal microscopy in mouse diaphragm motor nerve endings during septin polymerization induced by forchlorfenuron application. It was shown that forchlorfenuron application reduces neurotransmission during prolonged high-frequency (20 and 50 pulses/s) stimulation. Application of pairs of short high-frequency stimulation trains showed that forchlorfenuron slows the replenishment of the readily releasable pool. Forchlorfenuron enhanced FM 1-43 fluorescent dye loading by synaptic vesicle endocytosis but decreased dye unloading from the preliminarily stained nerve endings by synaptic vesicle exocytosis. It was concluded that the septin polymerization induced by forchlorfenuron application slows the rate of synaptic vesicle recycling in motor nerve endings due to the impairment of synaptic vesicle transport.

Impairment of Synaptic Vesicle Exocytosis and Recycling During Neuromuscular Weakness Produced in Mice by 2,4-Dithiobiuret

2002 ◽  
Vol 88 (6) ◽  
pp. 3243-3258 ◽  
Author(s):  
You-Fen Xu ◽  
Dawn Autio ◽  
Mary B. Rheuben ◽  
William D. Atchison
Keyword(s):  
Synaptic Vesicle ◽  
Muscle Weakness ◽  
Nerve Stimulation ◽  
Synaptic Vesicles ◽  
Motor Nerve ◽  
Neuromuscular Disorders ◽  
Neuroaxonal Dystrophy ◽  
Nerve Terminals ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis

Chronic treatment of rodents with 2,4-dithiobiuret (DTB) induces a neuromuscular syndrome of flaccid muscle weakness that mimics signs seen in several human neuromuscular disorders such as congenital myasthenic syndromes, botulism, and neuroaxonal dystrophy. DTB-induced muscle weakness results from a reduction of acetylcholine (ACh) release by mechanisms that are not yet clear. The objective of this study was to determine if altered release of ACh during DTB-induced muscle weakness was due to impairments of synaptic vesicle exocytosis, endocytosis, or internal vesicular processing. We examined motor nerve terminals in the triangularis sterni muscles of DTB-treated mice at the onset of muscle weakness. Uptake of FM1-43, a fluorescent marker for endocytosis, was reduced to approximately 60% of normal after either high-frequency nerve stimulation or K+depolarization. Terminals ranged from those with nearly normal fluorescence (“bright terminals”) to terminals that were poorly labeled (“dim terminals”). Ultrastructurally, the number of synaptic vesicles that were labeled with horseradish peroxidase (HRP) was also reduced by DTB to approximately 60%; labeling among terminals was similarly variable. A subset of DTB-treated terminals having abnormal tubulovesicular profiles in their centers did not respond to stimulation with increased uptake of HRP and may correspond to dim terminals. Two findings suggest that posttetanic “slow endocytosis” remained qualitatively normal: the rate of this type of endocytosis as measured with FM1-43 did not differ from normal, and HRP was observed in organelles associated with this pathway- coated vesicles, cisternae, as well as synaptic vesicles but not in the tubulovesicular profiles. In DTB-treated bright terminals, end-plate potential (EPP) amplitudes were decreased, and synaptic depression in response to 15-Hz stimulation was increased compared with those of untreated mice; in dim terminals, EPPs were not observed during block withd-tubocurarine. Nerve-stimulation-induced unloading of FM1-43 was slower and less complete than normal in bright terminals, did not occur in dim terminals, and was not enhanced by α-latrotoxin. Collectively, these results indicate that the size of the recycling vesicle pool is reduced in nerve terminals during DTB-induced muscle weakness. The mechanisms by which this reduction occurs are not certain, but accumulated evidence suggests that they may include defects in either or both exocytosis and internal vesicular processing.

scholarly journals Syntaxin 1B, but Not Syntaxin 1A, Is Necessary for the Regulation of Synaptic Vesicle Exocytosis and of the Readily Releasable Pool at Central Synapses

PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e90004 ◽  
Author(s):  
Tatsuya Mishima ◽  
Tomonori Fujiwara ◽  
Masumi Sanada ◽  
Takefumi Kofuji ◽  
Masami Kanai-Azuma ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Syntaxin 1A ◽  
Releasable Pool ◽  
Readily Releasable Pool ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis ◽  
Syntaxin 1B ◽  
Central Synapses

scholarly journals Otoferlin Depletion Results in Abnormal Synaptic Ribbons and Altered Intracellular Calcium Levels in Zebrafish

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Aayushi Manchanda ◽  
Paroma Chatterjee ◽  
Josephine A. Bonventre ◽  
Derik E. Haggard ◽  
Katie S. Kindt ◽  
...  
Keyword(s):  
Hair Cell ◽  
Synaptic Vesicle ◽  
Hair Cells ◽  
Calcium Binding ◽  
Synaptic Ribbons ◽  
Vesicle Recycling ◽  
Synaptic Vesicle Exocytosis ◽  
Expression Of Genes ◽  
Vesicle Exocytosis ◽  
The Impact

Abstract The protein otoferlin plays an essential role at the sensory hair cell synapse. Mutations in otoferlin result in deafness and depending on the species, mild to strong vestibular deficits. While studies in mouse models suggest a role for otoferlin in synaptic vesicle exocytosis and endocytosis, it is unclear whether these functions are conserved across species. To address this question, we characterized the impact of otoferlin depletion in zebrafish larvae and found defects in synaptic vesicle recycling, abnormal synaptic ribbons, and higher resting calcium concentrations in hair cells. We also observed abnormal expression of the calcium binding hair cell genes s100s and parvalbumin, as well as the nogo related proteins rtn4rl2a and rtn4rl2b. Exogenous otoferlin partially restored expression of genes affected by endogenous otoferlin depletion. Our results suggest that in addition to vesicle recycling, depletion of otoferlin disrupts resting calcium levels, alters synaptic ribbon architecture, and perturbs transcription of hair cells specific genes during zebrafish development.

scholarly journals Intracellular Acidification Suppresses Synaptic Vesicle Mobilization in the Motor Nerve Terminals

Acta Naturae ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 105-113
Author(s):  
A. L. Zefirov ◽  
R. D. Mukhametzyanov ◽  
A. V. Zakharov ◽  
K. A. Mukhutdinova ◽  
U. O. Odnoshivkina ◽  
...  
Keyword(s):  
Synaptic Vesicle ◽  
Neurotransmitter Release ◽  
Neuromuscular Junctions ◽  
Motor Nerve ◽  
Synaptic Activity ◽  
Special Role ◽  
Intracellular Acidification ◽  
Synaptic Vesicle Exocytosis ◽  
Vesicle Exocytosis ◽  
Cytoplasmic Acidification

Intracellular protons play a special role in the regulation of presynaptic processes, since the functioning of synaptic vesicles and endosomes depends on their acidification by the H+-pump. Furthermore, transient acidification of the intraterminal space occurs during synaptic activity. Using microelectrode recording of postsynaptic responses (an indicator of neurotransmitter release) and exo-endocytic marker FM1-43, we studied the effects of intracellular acidification with propionate on the presynaptic events underlying neurotransmitter release. Cytoplasmic acidification led to a marked decrease in neurotransmitter release during the first minute of a 20-Hz stimulation in the neuromuscular junctions of mouse diaphragm and frog cutaneous pectoris muscle. This was accompanied by a reduction in the FM1-43 loss during synaptic vesicle exocytosis in response to the stimulation. Estimation of the endocytic uptake of FM1-43 showed no disruption in synaptic vesicle endocytosis. Acidification completely prevented the action of the cell-membrane permeable compound 24-hydroxycholesterol, which can enhance synaptic vesicle mobilization. Thus, the obtained results suggest that an increase in [H+]in negatively regulates neurotransmission due to the suppression of synaptic vesicle delivery to the sites of exocytosis at high activity. This mechanism can be a part of the negative feedback loop in regulating neurotransmitter release.

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