Heterotrimeric Go protein links Wnt-Frizzled signaling with ankyrins to regulate the neuronal microtubule cytoskeleton.

Anne-Marie Lüchtenborg,Chen Lin,Gonzalo P Solis,Alexey Koval,Vladimir L Katanaev,Maxime G Blanchard,Stephan Kellenberger,Diane Egger-Adam

doi:10.1242/dev.106773

Anne-Marie Lüchtenborg, Chen Lin + Show 6 more

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https://doi.org/10.1242/dev.106773

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Abstract

Drosophila neuromuscular junctions (NMJs) represent a powerful model system with which to study glutamatergic synapse formation and remodeling. Several proteins have been implicated in these processes, including components of canonical Wingless (Drosophila Wnt1) signaling and the giant isoforms of the membrane-cytoskeleton linker Ankyrin 2, but possible interconnections and cooperation between these proteins were unknown. Here, we demonstrate that the heterotrimeric G protein Go functions as a transducer of Wingless-Frizzled 2 signaling in the synapse. We identify Ankyrin 2 as a target of Go signaling required for NMJ formation. Moreover, the Go-ankyrin interaction is conserved in the mammalian neurite outgrowth pathway. Without ankyrins, a major switch in the Go-induced neuronal cytoskeleton program is observed, from microtubule-dependent neurite outgrowth to actin-dependent lamellopodial induction. These findings describe a novel mechanism regulating the microtubule cytoskeleton in the nervous system. Our work in Drosophila and mammalian cells suggests that this mechanism might be generally applicable in nervous system development and function.

Highlights

Go is the most abundant heterotrimeric G protein in the central nervous system of both vertebrates and invertebrates (Sternweis and Robishaw, 1984; Wolfgang et al, 1990)
Synaptic plasticity underlies learning and memory. Both in invertebrates and vertebrates, activation of Wnt signaling is involved in several aspects of synapse formation and remodeling (Budnik and Salinas, 2011), and defects in this pathway may be causative of synaptic loss and neurodegeneration (Inestrosa and Arenas, 2010)
We further demonstrate that Ank2, a known player in the neuromuscular junctions (NMJs) (Koch et al, 2008; Pielage et al, 2008), is a target of Gαo in this signaling

Summary

Introduction

Go is the most abundant heterotrimeric G protein in the central nervous system of both vertebrates and invertebrates (Sternweis and Robishaw, 1984; Wolfgang et al, 1990). It is the immediate transducer of a number of G protein-coupled receptors (GPCRs), including receptors of the Frizzled (Fz) family (Egger-Adam and Katanaev, 2008). The intrinsic GTPase activity of Gα leads to hydrolysis of GTP to GDP; the resultant Gα-GDP can continue to signal or associates back with Gβγ to bind GPCRs (Gilman, 1987; Katanaev, 2010)

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