Abstract
BackgroundMyosin VI, encoded by jaguar (jar) in Drosophila melanogaster, is a unique member of the myosin superfamily of actin-based motor proteins. Myosin VI is the only myosin known to move towards the minus or pointed ends of actin filaments. Although Myosin VI has been implicated in numerous cellular processes as both an anchor and a transporter, little is known about the role of Myosin VI in the nervous system. We previously recovered jar in a screen for genes that modify neuromuscular junction (NMJ) development and here we report on the genetic analysis of Myosin VI in synaptic development and function using loss of function jar alleles.ResultsOur experiments on Drosophila third instar larvae revealed decreased locomotor activity, a decrease in NMJ length, a reduction in synaptic bouton number, and altered synaptic vesicle localization in jar mutants. Furthermore, our studies of synaptic transmission revealed alterations in both basal synaptic transmission and short-term plasticity at the jar mutant neuromuscular synapse.ConclusionsAltogether these findings indicate that Myosin VI is important for proper synaptic function and morphology. Myosin VI may be functioning as an anchor to tether vesicles to the bouton periphery and, thereby, participating in the regulation of synaptic vesicle mobilization during synaptic transmission.
Highlights
Myosin VI, encoded by jaguar in Drosophila melanogaster, is a unique member of the myosin superfamily of actin-based motor proteins
When the band density was measured for Myosin VI staining and normalized to the intensity of the loading control, btubulin, a reduction in Myosin VI levels was observed in two different heterozygote combinations, jar322/+ and Df(3R)crb87-5/+, as compared to the control in blots of both brain and body wall samples, this is less obvious on the blot
These data are representative of three separate trials of this experiment and serve to confirm the Myosin VI alleles used for this study were loss of function, consistent with previous descriptions of these alleles [32]
Summary
Myosin VI, encoded by jaguar (jar) in Drosophila melanogaster, is a unique member of the myosin superfamily of actin-based motor proteins. While many of the molecular mechanisms that regulate the synaptic vesicle cycle are becoming understood, the methods by which vesicles move within the nerve terminal are less well known. Understanding the mechanisms by which vesicles move within nerve terminals will inform our knowledge of both the exoand endocytic branches of the vesicle cycle. Two modes of transport can be envisioned: diffusion and active transport. Some studies, such as an analysis of vesicles in the recycling pool, are consistent with the notion that simple diffusion is a contributing force [4]. Several studies indicate that a myosin-based active transport mechanism may be important [2,5,6], there are some results to the contrary [7]
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