Wnt signaling establishes anteroposterior neuronal polarity and requires retromer in C. elegans.
Secreted Wnt proteins influence neural connectivity by regulating axon guidance, dendritic morphogenesis and synapse formation. We report a new role for Wnt and Frizzled proteins in establishing the anteroposterior polarity of the mechanosensory neurons ALM and PLM in C. elegans. Disruption of Wnt signaling leads to a complete inversion of ALM and PLM polarity: the anterior process adopts the length, branching pattern and synaptic properties of the wild-type posterior process, and vice versa. Different but overlapping sets of Wnt proteins regulate neuronal polarity in different body regions. Wnts act directly on PLM via the Frizzled LIN-17. In addition, we show that they are needed for axon branching and anteriorly directed axon growth. We also find that the retromer, a conserved protein complex that mediates transcytosis and endosome-to-Golgi protein trafficking, plays a key role in Wnt signaling. Deletion mutations of retromer subunits cause ALM and PLM polarity, and other Wnt-related defects. We show that retromer protein VPS-35 is required in Wnt-expressing cells and propose that retromer activity is needed to generate a fully active Wnt signal.
Molecular Neurobiology Program, Department of Pharmacology, Skirball Institute, NYU School of Medicine, New York, NY 10016, USA.
Brinda C
BC
Prasad
Scott G
SG
Clark
D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D016764:Cell Polarity; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D009475:Neurons, Afferent / Q000166:cytology / Q000502:physiology; D034622:RNA Interference; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000235:genetics; D051153:Wnt Proteins / Q000235:genetics / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; C101684:LIN-17 protein, C elegans; D043562:Receptors, G-Protein-Coupled; C511108:VPS-35 protein, C elegans; C419573:VPS35 protein, human; D033921:Vesicular Transport Proteins; D051153:Wnt Proteins; D049452:Green Fluorescent Proteins