title: Heterotrimeric Go protein links Wnt-Frizzled signaling with ankyrins to regulate the neuronal microtubule cytoskeleton.
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.
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 27, Lausanne 1005, Switzerland Department of Biology, University of Konstanz, Universitätsstrasse 10, Box 643, Konstanz 78457, Germany.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lüchtenborg
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 27, Lausanne 1005, Switzerland.
authors.forename: Gonzalo P
authors.initials: GP
authors.lastname: Solis
authors.affiliation: Department of Biology, University of Konstanz, Universitätsstrasse 10, Box 643, Konstanz 78457, Germany.
authors.forename: Diane
authors.initials: D
authors.lastname: Egger-Adam
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 27, Lausanne 1005, Switzerland.
authors.forename: Alexey
authors.initials: A
authors.lastname: Koval
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 27, Lausanne 1005, Switzerland Department of Biology, University of Konstanz, Universitätsstrasse 10, Box 643, Konstanz 78457, Germany.
authors.forename: Chen
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 27, Lausanne 1005, Switzerland.
authors.forename: Maxime G
authors.initials: MG
authors.lastname: Blanchard
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 27, Lausanne 1005, Switzerland.
authors.forename: Stephan
authors.initials: S
authors.lastname: Kellenberger
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Biology and Medicine, University of Lausanne, Rue du Bugnon 27, Lausanne 1005, Switzerland Department of Biology, University of Konstanz, Universitätsstrasse 10, Box 643, Konstanz 78457, Germany vladimir.katanaev@unil.ch.
authors.forename: Vladimir L
authors.initials: VL
authors.lastname: Katanaev
mesh_terms: D000818:Animals; D017487:Ankyrins / Q000378:metabolism*; D002460:Cell Line; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000378:metabolism*; D051157:Frizzled Receptors / Q000378:metabolism*; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000378:metabolism*; D008322:Mammals; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D011485:Protein Binding; D015398:Signal Transduction; D013569:Synapses / Q000378:metabolism; D051155:Wnt1 Protein / Q000378:metabolism*
chemical_list: C498993:Ank2 protein, Drosophila; D017487:Ankyrins; D029721:Drosophila Proteins; D051157:Frizzled Receptors; D051155:Wnt1 Protein; C101703:fz2 protein, Drosophila; C074622:wg protein, Drosophila; D019206:GTP-Binding Protein alpha Subunits, Gi-Go
keywords: Ankyrin; Drosophila; Frizzled; G protein; Microtubules; Neuromuscular junction; Wnt