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Thesis

French

ID: <

10670/1.5xokrb

>

Where these data come from
Role of MAP1/Futsch in synapse organization and functioning at the drosophila neuromuscular junction

Abstract

Structural microtubule associated proteins like those belonging to the MAP1 family are known to control the stability and dynamics of microtubules (MTs). They are also known to interact with postsynaptic proteins like GABA or glutamate receptors. However, their presynaptic role in neurotransmitter release was barely studied. Here, we took advantage of the Drosophila model in which there is only one MAP1 homologue, called Futsch. We studied the function of Futsch at the larval neuromuscular junction (NMJ), where this protein is found presynaptically only. Here, we show that, in addition to its known function on NMJ morphology (Roos et al., 2000; Gogel et al., 2006), Futsch is also important for NMJ physiology, by controlling neurotransmitter release as well as active zone density. We show that this physiological effect of Futsch is not the consequence of disrupted microtubule bundle and disrupted axonal transport, but must be the consequence of a local effect of Futsch at the synaptic terminal. We used 3D-Structured Illumination Microscopy (3D-SIM) to further study the localization of Futsch and MTs with respect to active zones. Both Futsch and MTs are almost systematically present in close proximity active zones, with Futsch being localized in-between MTs and active zones. Using proximity ligation assays, we further demonstrated the functional proximity of Futsch, but not MTs, with the active zone component Bruchpilot. Altogether our data are in favor of a model by which Futsch locally stabilizes active zones, by reinforcing their link with the underlying MT cytoskeleton.

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