Abstract
Synaptic vesicles dock on the presynaptic plasma membrane of axon terminals and become ready to fuse with the presynaptic membrane or primed. Fusion of the vesicle membrane and presynaptic membrane results in the formation of a pore between the membranes, through which the vesicle’s neurotransmitter is released into the synaptic cleft. A recent electron tomography study on frog neuromuscular junctions fixed at rest showed that there is no discernible gap between or merging of the membrane of docked synaptic vesicles with the presynaptic membrane, however, the extent of the contact area between the membrane of docked synaptic vesicles and the presynaptic membrane varies 10-fold with a normal distribution. The study also showed that when the neuromuscular junctions are fixed during repetitive electrical nerve stimulation, the portion of large contact areas in the distribution is reduced compared to the portion of small contact areas, suggesting that docked synaptic vesicles with the largest contact areas are greatly primed to fuse with the membrane. Furthermore, the finding of several hemifused synaptic vesicles among the docked vesicles was briefly reported. Here, the spatial relationship of 81 synaptic vesicles with the presynaptic membrane at active zones of the neuromuscular junctions fixed during stimulation is described in detail. For the most of the vesicles, the combined thickness of each of their contact sites was not different from the sum of the membrane thicknesses of the vesicle membrane and presynaptic membrane, similar to the docked vesicles at active zones of the resting neuromuscular junctions. However, the combined membrane thickness of a small portion of the vesicles was considerably less than the sum of the membrane thicknesses, indicating that the membranes at their contact sites were fixed in a state of hemifusion. Moreover, the hemifused vesicles were found to have large contact areas with the presynaptic membrane. These findings support the recently proposed hypothesis that, at frog neuromuscular junctions, docked synaptic vesicles with the largest contact areas are most primed for fusion with the presynaptic membrane, and that hemifusion is a fusion intermediate step of the vesicle membrane with the presynaptic membrane for synaptic transmission.
Highlights
Synaptic vesicles are docked or held at specialized regions, called active zones, on the presynaptic plasma membrane [1,2]
Previous studies on resting frog neuromuscular junctions (NMJs) using electron tomography found no evidence of hemifused synaptic vesicles at active zones, raising some concerns as to whether synaptic vesicles go through hemifusion prior to fusion with the presynaptic membrane
34 reconstructed volumes of randomly selected axon terminals of frog NMJs fixed during evoked synaptic activity were generated, and more than 80 synaptic vesicles at active zones of the NMJs were examined, using serial virtual slices (
Summary
Synaptic vesicles are docked or held at specialized regions, called active zones, on the presynaptic plasma membrane [1,2]. Previous studies on resting frog neuromuscular junctions (NMJs) using electron tomography found no evidence of hemifused synaptic vesicles at active zones, raising some concerns as to whether synaptic vesicles go through hemifusion prior to fusion with the presynaptic membrane. A recent electron tomography study explored synaptic vesicles at active zones of axon terminals in frog NMJs, chemically fixed at rest and during electrical stimulation at 10 Hz [45] This chemical fixation method has been used to capture synaptic vesicles undergoing a variety of processes during evoked synaptic activity; synaptic vesicles at active zones are found to be docked, undocked, or fused with the presynaptic membrane [3,46,47]. The nanometer-scale quantification of the spatial relationship of synaptic vesicles with the presynaptic membrane by electron tomography may provide further understanding about the synaptic vesicle fusion pathway
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
