Tao kinases as coordinators of actin and microtubule dynamics in developing neurons

Abstract

Drosophila tao, encoding a Ste20 family kinase, was identified as a gene involved in ethanol, cocaine, and nicotine sensitivity. The behavioral phenotypes appear to be caused by defects in the development of the adult brain. Specifically, Drosophila tao functions to promote axon guidance of mushroom body (MB) neurons. The MB is a large structure in the central brain of the fly whose development and function have been well characterized. tao interacts genetically with mutations in the par-1 gene, also encoding a serine-threonine kinase. Since Par-1 has been implicated in the regulation of microtubule dynamics, this suggests that tao regulates the microtubule cytoskeleton in developing MB neurons. Here we discuss these results in light of previous studies that have proposed that Drosophila tao and its mammalian homologues function as a link between the actin and microtubule cytoskeletons, regulating microtubule stability in response to actin signals.

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Figures and Tables

Figure 1 Axon guidance defects in Drosophila tao mutants. (A) The neurons of the mushroom bodies send axon projections from cell bodies in the posterior of the brain. Mushroom body axons form a fasciculated bundle (the peduncle), which branches into three sets of lobes in the anterior of the brain. (B) Mushroom body lobes, visualized with an antibody to Fasciclin II in a wild-type brain and (C) in the brain of a tao mutant fly. In the tao mutant, mushroom body axons fail to follow their proscribed paths to the anterior regions of the brain, instead massing near the cell bodies in the posterior.

Figure 2 Possible function of Drosophila Tao in cytoskeletal control pathways. (A) Studies of mushroom body development indicate that Drosophila tao acts with par-1 to control phosphorylation of the microtubule binding protein Tau, while in vitro studies suggest that tao may directly stabilize microtubules in response to signals from the actin cytoskeleton. Studies in mammals and Drosophila also suggest that Tao kinases may integrate signals from a number of other upstream sources, such as growth factor receptors and cell-adhesion molecules. (B) Combining these results, we propose that tao might mediate interactions between the actin and microtubule cytosketons in extending growth cones as well, leading to axon guidance defects observed in Drosophila tao mutants. Signals from filopodial actin may act through tao to stabilize and capture extending microtubules.

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