PMID- 30738855 OWN - NLM STAT- MEDLINE DCOM- 20191224 LR - 20191224 IS - 1873-7544 (Electronic) IS - 0306-4522 (Linking) VI - 404 DP - 2019 Apr 15 TI - Reorganization of Septins Modulates Synaptic Transmission at Neuromuscular Junctions. PG - 91-101 LID - S0306-4522(19)30087-9 [pii] LID - 10.1016/j.neuroscience.2019.01.060 [doi] AB - 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 Ca(2+) influx but is likely related to the impairment of later stages occurring after Ca(2+) 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. CI - Copyright (c) 2019 IBRO. Published by Elsevier Ltd. All rights reserved. FAU - Nurullin, Leniz F AU - Nurullin LF AD - Laboratory of Biophysics Of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, Kazan, Russia; Kazan State Medical University, Kazan, Russia; Open Laboratory of Neuropharmacology, Kazan Federal University, Kazan, Russia. Electronic address: rus_science@yahoo.com. FAU - Khuzakhmetova, Venera F AU - Khuzakhmetova VF AD - Laboratory of Biophysics Of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, Kazan, Russia; Open Laboratory of Neuropharmacology, Kazan Federal University, Kazan, Russia. FAU - Khaziev, Eduard F AU - Khaziev EF AD - Laboratory of Biophysics Of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, Kazan, Russia; Open Laboratory of Neuropharmacology, Kazan Federal University, Kazan, Russia; A.N. Tupolev Kazan National Research Technical University, Kazan, Russia. FAU - Samigullin, Dmitry V AU - Samigullin DV AD - Laboratory of Biophysics Of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, Kazan, Russia; Open Laboratory of Neuropharmacology, Kazan Federal University, Kazan, Russia; A.N. Tupolev Kazan National Research Technical University, Kazan, Russia. FAU - Tsentsevitsky, Andrei N AU - Tsentsevitsky AN AD - Laboratory of Biophysics Of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, Kazan, Russia. FAU - Skorinkin, Andrei I AU - Skorinkin AI AD - Laboratory of Biophysics Of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, Kazan, Russia. FAU - Bukharaeva, Ellya A AU - Bukharaeva EA AD - Laboratory of Biophysics Of Synaptic Processes, Kazan Institute of Biochemistry and Biophysics, FRC Kazan Scientific Center of RAS, Kazan, Russia; Open Laboratory of Neuropharmacology, Kazan Federal University, Kazan, Russia. FAU - Vagin, Olga AU - Vagin O AD - Department of Physiology, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA; Veterans Administration Greater Los Angeles Healthcare System, Los Angeles, CA, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190208 PL - United States TA - Neuroscience JT - Neuroscience JID - 7605074 RN - EC 3.6.1.- (Septins) SB - IM MH - Animals MH - Diaphragm/innervation/physiology MH - Evoked Potentials, Motor/*physiology MH - Mice MH - Mice, Inbred BALB C MH - Neuromuscular Junction/*pathology MH - Phrenic Nerve/physiology MH - Septins/*physiology MH - Synapses/*physiology MH - Synaptic Transmission/*physiology OTO - NOTNLM OT - acetylcholine quantal release OT - calcium imaging OT - neuromuscular junction OT - septins EDAT- 2019/02/11 06:00 MHDA- 2019/12/25 06:00 CRDT- 2019/02/11 06:00 PHST- 2018/07/06 00:00 [received] PHST- 2019/01/27 00:00 [revised] PHST- 2019/01/29 00:00 [accepted] PHST- 2019/02/11 06:00 [pubmed] PHST- 2019/12/25 06:00 [medline] PHST- 2019/02/11 06:00 [entrez] AID - S0306-4522(19)30087-9 [pii] AID - 10.1016/j.neuroscience.2019.01.060 [doi] PST - ppublish SO - Neuroscience. 2019 Apr 15;404:91-101. doi: 10.1016/j.neuroscience.2019.01.060. Epub 2019 Feb 8.