scholarly journals Tetanus neurotoxin sensitive SNARE-mediated glial signaling limits motoneuronal excitability

2020 ◽  
Author(s):  
Mathias A. Böhme ◽  
Anthony W. McCarthy ◽  
Monika Berezeckaja ◽  
Kristina Ponimaskin ◽  
Alexander M. Walter

AbstractPeripheral nerves contain motoneuron axons coated by glial cells, which essentially contribute to function but cellular reactions remain poorly understood. We here identify non-neuronal Synaptobrevin (Syb) as the essential vesicular SNARE in glia to insulate and metabolically supply Drosophila motoneurons. Interfering with Syb-functionality by glial knockdown, or glial expression of tetanus neurotoxin light chain (TeNT-LC) caused motonerve disintegration, blocked axonal transport, induced tetanic muscle hyperactivity and caused lethal paralysis. Surprisingly, not the established TeNT-LC-target, neuronal Synaptobrevin (nSyb), is the relevant SNARE, but non-neuronal Synaptobrevin (Syb): Knockdown of Syb- (but not nSyb-) phenocopied glial TeNT-LC expression whose effects were reverted by a TeNT-LC-insensitive Syb mutant. We link Syb-necessity to two distinct glia: to establish nerve insulating septate junctions in subperineurial glia and to integrate monocarboxylate transporters along the nerve in wrapping glia for motoneuronal metabolic supply. Our study identifies crucial roles of Syb in glial subtypes for nerve function and pathology, animal motility and survival.

1977 ◽  
Vol 23 (1) ◽  
pp. 315-324
Author(s):  
N.J. Lane ◽  
L.S. Swales ◽  
N.J. Abbott

Central neural connectives and peripheral nerves from the crayfish Procambarus clarkii were incubated in 5 mM lanthanum solutions in physiological saline, for periods from 15 min to 2 h. The tracer only rarely reaches the axon surfaces in the perineurium-ensheathed connectives, penetrating the elaborate perineurial layer slowly. In peripheral nerves, on the other hand, where the perineurium is extermely attenuated and interrupted by open extracellular clefts, inward movement of lanthanum to the axon surfaces occurs readily. When the perineurial layer of the neural connectives is removed by ‘desheathing’, penetration of the tracer to the level of the axolemma occurs rapidly, implicating the perineurium as the major site of restriction of entry of large ions and exogenous molecules. This conclusion is discussed in relation to recent electrophysiological studies on K+ movements. In both peripheral nerves and desheathed connectives, the transcellular tubular lattice system present in crustacean glial cells appears to serve as a route for the entry of tracer to the axon surfaces, and is more direct than the long and complex extracellular pathway formed by the interdigitations of the extensive glial cell processes.


1979 ◽  
Vol 160 (1) ◽  
pp. 196-202 ◽  
Author(s):  
L. Di Giamberardino ◽  
J.Y. Couraud ◽  
E.A. Barnard

2000 ◽  
Vol 11 (6) ◽  
pp. 2161-2173 ◽  
Author(s):  
Ming-Ying Tsai ◽  
Gerardo Morfini ◽  
Györgyi Szebenyi ◽  
Scott T. Brady

The nature of kinesin interactions with membrane-bound organelles and mechanisms for regulation of kinesin-based motility have both been surprisingly difficult to define. Most kinesin is recovered in supernatants with standard protocols for purification of motor proteins, but kinesin recovered on membrane-bound organelles is tightly bound. Partitioning of kinesin between vesicle and cytosolic fractions is highly sensitive to buffer composition. Addition of eitherN-ethylmaleimide or EDTA to homogenization buffers significantly increased the fraction of kinesin bound to organelles. Given that an antibody against kinesin light chain tandem repeats also releases kinesin from vesicles, these observations indicated that specific cytoplasmic factors may regulate kinesin release from membranes. Kinesin light tandem repeats contain DnaJ-like motifs, so the effects of hsp70 chaperones were evaluated. Hsc70 released kinesin from vesicles in an MgATP-dependent andN-ethylmaleimide-sensitive manner. Recombinant kinesin light chains inhibited kinesin release by hsc70 and stimulated the hsc70 ATPase. Hsc70 actions may provide a mechanism to regulate kinesin function by releasing kinesin from cargo in specific subcellular domains, thereby effecting delivery of axonally transported materials.


2018 ◽  
Author(s):  
Nathan McDannold ◽  
Yongzhi Zhang ◽  
Chanikarn Power ◽  
Natalia Vykhodtseva

The goal of this work will be to investigate the safety of ablating tissue with focused ultrasound adjacent to peripheral nerves or to nerve tracts in the brain. We propose experiments in which we ablate tissue adjacent to the sciatic nerve and the optic nerve/tract in the brain and then evaluate nerve function. These experiments are motivated by two promising targets for focused ultrasound treatment where critical nerve structures need to be protected: prostate cancer and brain tumors. If successful, this work will allow good surgical margins, thereby improving the effectiveness of focused ultrasound surgery and reducing local recurrence.


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