C. Elegans AP-2 and Retromer Control Wnt Signaling by Regulating mig-14/Wntless

Dev Cell. 2008 Jan;14(1):132-9. doi: 10.1016/j.devcel.2007.12.001. Epub 2007 Dec 20.

Abstract

While endocytosis can regulate morphogen distribution, its precise role in shaping these gradients is unclear. Even more enigmatic is the role of retromer, a complex that shuttles proteins between endosomes and the Golgi apparatus, in Wnt gradient formation. Here we report that DPY-23, the C. elegans mu subunit of the clathrin adaptor AP-2 that mediates the endocytosis of membrane proteins, regulates Wnt function. dpy-23 mutants display Wnt phenotypes, including defects in neuronal migration, neuronal polarity, and asymmetric cell division. DPY-23 acts in Wnt-expressing cells to promote these processes. MIG-14, the C. elegans homolog of the Wnt-secretion factor Wntless, also acts in these cells to control Wnt function. In dpy-23 mutants, MIG-14 accumulates at or near the plasma membrane. By contrast, MIG-14 accumulates in intracellular compartments in retromer mutants. Based on our observations, we propose that intracellular trafficking of MIG-14 by AP-2 and retromer plays an important role in Wnt secretion.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptor Protein Complex 2 / genetics
  • Adaptor Protein Complex 2 / physiology*
  • Animals
  • Axons / physiology
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / physiology*
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Endocytosis
  • Homeostasis
  • Intracellular Signaling Peptides and Proteins
  • Mutation
  • Oligonucleotide Array Sequence Analysis
  • Phenotype
  • Transcription Factor AP-2 / physiology*
  • Wnt Proteins / physiology*

Substances

  • Adaptor Protein Complex 2
  • Caenorhabditis elegans Proteins
  • Carrier Proteins
  • Dpy-23 protein, C elegans
  • Intracellular Signaling Peptides and Proteins
  • Mig-14 protein, C elegans
  • Transcription Factor AP-2
  • Wnt Proteins