Reorganization of Septins Modulates Synaptic Transmission at Neuromuscular Junctions

• Published in: Neuroscience 2019-04, Vol.404, p.91-101
• Main Authors: Nurullin, Leniz F., Khuzakhmetova, Venera F., Khaziev, Eduard F., Samigullin, Dmitry V., Tsentsevitsky, Andrei N., Skorinkin, Andrei I., Bukharaeva, Ellya A., Vagin, Olga
• Format: Article
• Language: English
• Subjects: acetylcholine quantal release; Animals; calcium imaging; Diaphragm - innervation; Diaphragm - physiology; Evoked Potentials, Motor - physiology; Mice; Mice, Inbred BALB C; neuromuscular junction; Neuromuscular Junction - pathology; Phrenic Nerve - physiology; septins; Septins - physiology; Synapses - physiology; Synaptic Transmission - physiology
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2019.01.060

Septins (Sept) are highly conserved Guanosine-5'-triphosphate (GTP)-binding cytoskeletal proteins involved in neuronal signaling in the central nervous system but their involvement in signal transmission in peripheral synapses remains unclear. Sept5 and Sept9 proteins were detected in mouse peripheral neuromuscular junctions by immunofluorescence with a greater degree of co-localization with presynaptic than postsynaptic membranes. Preincubation of neuromuscular junction preparations with the inhibitor of Sept dynamics, forchlorfenuron (FCF), decreased co-localization of Sept with presynaptic membranes. FCF introduced ex vivo or in vivo had no effect on the amplitude of the spontaneous endplate currents (EPCs), indicating the absence of postsynaptic effects of FCF. However, FCF decreased acetylcholine (ACh) quantal release in response to nerve stimulation, reduced the amplitude of evoked quantal currents and decreased the number of quanta with long synaptic delays, demonstrating the presynaptic action of FCF. Nevertheless, FCF had no effect on the amplitude of calcium transient in nerve terminals, as detected by calcium-sensitive dye, and slightly decreased the ratio of the second response amplitude to the first one in paired-pulse experiments. These results suggest that FCF-induced decrease in ACh quantal secretion is not due to a decrease in Ca2+ influx but is likely related to the impairment of later stages occurring after Ca2+ entry, such as trafficking, docking or membrane fusion of synaptic vesicles. Therefore, Sept9 and Sept5 are abundantly expressed in presynaptic membranes, and disruption of Sept dynamics suppresses the evoked synchronous and delayed asynchronous quantal release of ACh, strongly suggesting an important role of Sept in the regulation of neurotransmission in peripheral synapses. •Sept9 and Sept5 expressed in the presynaptic region in the neuromuscular junctions•FCF inhibits the neurotransmitter quantal release.•FCF alters temporal parameters of quantal release.•FCF did not change calcium ion influx into the nerve terminals.•Septins play a functional role in maintenance of reliability of synaptic transmission.