Vesicular Axonal Transport is Modified In Vivo by Tau Deletion or Overexpression in Drosophila.

Yasmina Talmat-Amar,Marie-Laure Parmentier,Yoan Arribat

doi:10.3390/ijms19030744

Abstract

Structural microtubule associated protein Tau is found in high amount in axons and is involved in several neurodegenerative diseases. Although many studies have highlighted the toxicity of an excess of Tau in neurons, the in vivo understanding of the endogenous role of Tau in axon morphology and physiology is poor. Indeed, knock-out mice display no strong cytoskeleton or axonal transport phenotype, probably because of some important functional redundancy with other microtubule-associated proteins (MAPs). Here, we took advantage of the model organism Drosophila, which genome contains only one homologue of the Tau/MAP2/MAP4 family to decipher (endogenous) Tau functions. We found that Tau depletion leads to a decrease in microtubule number and microtubule density within axons, while Tau excess leads to the opposite phenotypes. Analysis of vesicular transport in tau mutants showed altered mobility of vesicles, but no change in the total amount of putatively mobile vesicles, whereas both aspects were affected when Tau was overexpressed. In conclusion, we show that loss of Tau in tau mutants not only leads to a decrease in axonal microtubule density, but also impairs axonal vesicular transport, albeit to a lesser extent compared to the effects of an excess of Tau.

Highlights

Axons are specific cellular structures extending along large distances in adult organisms
We found that Tau depletion leads to a decrease in microtubule number and microtubule density within axons, while Tau excess leads to the opposite phenotypes
To investigate the role of endogenous Drosophila Tau in axons, especially its role in axonal transport, we focused on the segmental nerves of Drosophila larvae

Summary

Introduction

Axons are specific cellular structures extending along large distances in adult organisms. Their integrity requires a robust cytoskeleton, which enables anterograde and retrograde active transport between the soma and the synaptic terminals. Microtubules (MTs) are the tracks required for axonal transport and their organization and stability are controlled by different structural microtubule-associated proteins (MAPs). The MAP2/Tau family contains three genes in Vertebrates encoding the proteins MAP2, MAP4, and Tau [1]. These proteins contain a similar microtubule-binding domain, responsible for microtubule stabilization and bundling [2,3,4,5]. Numerous in vitro studies or studies based on overexpression of these proteins indicated that they are able to promote MT polymerization, MT stabilization, and MT bundling [6,7,8,9,10]

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