Abstract
Drosophila Ringmaker (Ringer) is homologous to the human Tubulin Polymerization Promoting Proteins (TPPPs) that are implicated in the stabilization and bundling of microtubules (MTs) that are particularly important for neurons and are also implicated in synaptic organization and plasticity. No in vivo functional data exist that have addressed the role of TPPP in synapse organization in any system. Here, we present the phenotypic and functional characterization of ringer mutants during Drosophila larval neuromuscular junction (NMJ) synaptic development. ringer mutants show reduced synaptic growth and transmission and display phenotypic similarities and genetic interactions with the Drosophila homolog of vertebrate Microtubule Associated Protein (MAP)1B, futsch. Immunohistochemical and biochemical analyses show that individual and combined loss of Ringer and Futsch cause a significant reduction in MT loops at the NMJs and reduced acetylated-tubulin levels. Presynaptic over-expression of Ringer and Futsch causes elevated levels of acetylated-tubulin and significant increase in NMJ MT loops. These results indicate that Ringer and Futsch regulate synaptic MT organization in addition to synaptic growth. Together our findings may inform studies on the close mammalian homolog, TPPP, and provide insights into the role of MTs and associated proteins in synapse growth and organization.
Highlights
The establishment of proper neuronal connectivity in the nervous system is central to our cognition and behavior
Since Ringer is the Drosophila homolog of the human Tubulin Polymerization Promoting Proteins (TPPPs) family of proteins, we examined whether Ringer displayed any colocalization with Tubulin at the neuromuscular junction (NMJ)
Our studies reported here identify the Drosophila TPPP/Ringer in regulating presynaptic MT organization, stability and synaptic growth in concert with the Drosophila MAP1B/Futsch
Summary
The establishment of proper neuronal connectivity in the nervous system is central to our cognition and behavior. Classical microtubule-associated proteins (MAPs) perform a wide range of functions to regulate MT dynamics for properly organizing and remodeling the neuronal cytoskeleton (Ramkumar et al, 2018). The only Drosophila homolog of vertebrate MAP1B, Futsch, is necessary for dendritic, axonal and synaptic MT organization and growth (Hummel et al, 2000; Roos et al, 2000). Recent studies on Drosophila futsch have uncovered its role in stabilizing active zones (AZs) by reinforcing their link with the underlying MT cytoskeleton and in regulating neurotransmitter release at the NMJ (Lepicard et al, 2014) as well as activity dependent AZ remodeling of photoreceptor synapses (Sugie et al, 2015)
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