C. elegans AP-2 and retromer control Wnt signaling by regulating mig-14/Wntless.
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.
Pan
Chun-Liang
CL
Helen Wills Neuroscience Institute, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720-3204, USA.
Baum
Paul D
PD
Gu
Mingyu
M
Jorgensen
Erik M
EM
Clark
Scott G
SG
Garriga
Gian
G
D033962:Adaptor Protein Complex 2 / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001369:Axons / Q000502:physiology; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D004705:Endocytosis; D006706:Homeostasis; D047908:Intracellular Signaling Peptides and Proteins; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D050656:Transcription Factor AP-2 / Q000502:physiology*; D051153:Wnt Proteins / Q000502:physiology*
D033962:Adaptor Protein Complex 2; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; C527887:Dpy-23 protein, C elegans; D047908:Intracellular Signaling Peptides and Proteins; C527888:Mig-14 protein, C elegans; D050656:Transcription Factor AP-2; D051153:Wnt Proteins