Sphingomyelinase modulates synaptic vesicle mobilization at the mice neuromuscular junctions.

Autor: Tsentsevitsky AN; Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Federal Research Center 'Kazan Scientific Center of RAS', 2/31 Lobachevsky St, Box 30, Kazan, RT 420111, Russia., Gafurova CR; Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Federal Research Center 'Kazan Scientific Center of RAS', 2/31 Lobachevsky St, Box 30, Kazan, RT 420111, Russia., Mukhutdinova KA; Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Federal Research Center 'Kazan Scientific Center of RAS', 2/31 Lobachevsky St, Box 30, Kazan, RT 420111, Russia., Giniatullin AR; Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Federal Research Center 'Kazan Scientific Center of RAS', 2/31 Lobachevsky St, Box 30, Kazan, RT 420111, Russia; Kazan State Medial University, 49 Butlerova St., Kazan, RT 420012, Russia., Fedorov NS; Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Federal Research Center 'Kazan Scientific Center of RAS', 2/31 Lobachevsky St, Box 30, Kazan, RT 420111, Russia., Malomouzh AI; Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Federal Research Center 'Kazan Scientific Center of RAS', 2/31 Lobachevsky St, Box 30, Kazan, RT 420111, Russia., Petrov AM; Laboratory of Biophysics of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, Federal Research Center 'Kazan Scientific Center of RAS', 2/31 Lobachevsky St, Box 30, Kazan, RT 420111, Russia; Kazan State Medial University, 49 Butlerova St., Kazan, RT 420012, Russia. Electronic address: alexey.petrov@kazangmu.ru.
Jazyk: angličtina
Zdroj: Life sciences [Life Sci] 2023 Apr 01; Vol. 318, pp. 121507. Date of Electronic Publication: 2023 Feb 18.
DOI: 10.1016/j.lfs.2023.121507
Abstrakt: Aims: Sphingomyelin is an abundant component of the presynaptic membrane and an organizer of lipid rafts. In several pathological conditions, sphingomyelin is hydrolyzed due to an upregulation and release of secretory sphingomyelinases (SMases). Herein, the effects of SMase on exocytotic neurotransmitter release were studied in the diaphragm neuromuscular junctions of mice.
Main Methods: Microelectrode recordings of postsynaptic potentials and styryl (FM) dyes were used to estimate neuromuscular transmission. Membrane properties were assessed with fluorescent techniques.
Key Findings: Application of SMase at a low concentration (0.01 U ml -1 ) led to a disruption of lipid-packing in the synaptic membranes. Neither spontaneous exocytosis nor evoked neurotransmitter release (in response to single stimuli) were affected by SMase treatment. However, SMase significantly increased neurotransmitter release and the rate of fluorescent FM-dye loss from the synaptic vesicles at 10, 20 and 70 Hz stimulation of the motor nerve. In addition, SMase treatment prevented a shift of the exocytotic mode from "full-collapse" fusion to "kiss-and-run" during high-frequency (70 Hz) activity. The potentiating effects of SMase on neurotransmitter release and FM-dye unloading were suppressed when synaptic vesicle membranes were also exposed to this enzyme (i.e., stimulation occurred during SMase treatment).
Significance: Thus, hydrolysis of the plasma membrane sphingomyelin can enhance mobilization of synaptic vesicles and facilitate full fusion mode of exocytosis, but SMase acting on vesicular membrane had a depressant effect on the neurotransmission. Partially, the effects of SMase can be related with the changes in synaptic membrane properties and intracellular signaling.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. All authors consent to publish the article.
(Copyright © 2023 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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