Key result
Myosin VI loss-of-function mutations in Drosophila resulted in mislocalization of actively cycling synaptic vesicles and significantly enhanced vesicle mobility compared to controls (p<0.0001).
In a Drosophila model, Myosin VI is essential for tethering synaptic vesicles to the bouton periphery, restricting their mobility.
This is the authors' abstract. We don't add key points for this paper.
BACKGROUND: At the Drosophila neuromuscular junction (NMJ), synaptic vesicles are mobile; however, the mechanisms that regulate vesicle traffic at the nerve terminal are not fully understood. Myosin VI has been shown to be important for proper synaptic physiology and morphology at the NMJ, likely by functioning as a vesicle tether. Here we investigate vesicle dynamics in Myosin VI mutants of Drosophila. RESULTS: In Drosophila, Myosin VI is encoded by the gene, jaguar (jar). To visualize active vesicle cycling we used FM dye loading and compared loss of function alleles of jar with controls. These studies revealed a differential distribution of vesicles at the jar mutant nerve terminal, with the newly endocytosed vesicles observed throughout the mutant boutons in contrast to the peripheral localization visualized at control NMJs. This finding is consistent with a role for Myosin VI in restraining vesicle mobility at the synapse to ensure proper localization. To further investigate regulation of vesicle dynamics by Myosin VI, FRAP analysis was used to analyze movement of GFP-labeled synaptic vesicles within individual boutons. FRAP revealed that synaptic vesicles are moving more freely in the jar mutant boutons, indicated by changes in initial bleach depth and rapid recovery of fluorescence following photobleaching. CONCLUSION: This data provides insights into the role for Myosin VI in mediating synaptic vesicle dynamics at the nerve terminal. We observed mislocalization of actively cycling vesicles and an apparent increase in vesicle mobility when Myosin VI levels are reduced. These observations support the notion that a major function of Myosin VI in the nerve terminal is tethering synaptic vesicles to proper sub-cellular location within the bouton.
No immediate clinical implications; leaves open Myosin VI's role in mammalian synaptic vesicle dynamics.
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Kisiel et al. (2014) studied Myosin VI mutation. Myosin VI loss of function mutation (jar alleles) vs. Wild-type controls (Oregon R) was evaluated on Synaptic vesicle mobility (fluorescence recovery after photobleaching) (p=<0.0001). Myosin VI loss-of-function mutations in Drosophila resulted in mislocalization of actively cycling synaptic vesicles and significantly enhanced vesicle mobility compared to controls (p<0.0001).
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