The clathrin adaptor AP-1 complex and Arf1 regulate planar cell polarity in vivo

Nat Commun. 2015 Apr 7;6:6751. doi: 10.1038/ncomms7751.

Abstract

A key step in generating planar cell polarity (PCP) is the formation of restricted junctional domains containing Frizzled/Dishevelled/Diego (Fz/Dsh/Dgo) or Van Gogh/Prickle (Vang/Pk) complexes within the same cell, stabilized via Flamingo (Fmi) across cell membranes. Although models have been proposed for how these complexes acquire and maintain their polarized localization, the machinery involved in moving core PCP proteins around cells remains unknown. We describe the AP-1 adaptor complex and Arf1 as major regulators of PCP protein trafficking in vivo. AP-1 and Arf1 disruption affects the accumulation of Fz/Fmi and Vang/Fmi complexes in the proximo-distal axis, producing severe PCP phenotypes. Using novel tools, we demonstrate a direct and specific Arf1 involvement in Fz trafficking in vivo. Moreover, we uncover a conserved Arf1 PCP function in vertebrates. Our data support a model whereby the trafficking machinery plays an important part during PCP establishment, promoting formation of polarized PCP-core complexes in vivo.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADP-Ribosylation Factor 1 / genetics*
  • Adaptor Protein Complex 1 / genetics*
  • Adaptor Proteins, Signal Transducing / metabolism
  • Animals
  • Animals, Genetically Modified
  • Cadherins / metabolism
  • Carrier Proteins / metabolism
  • Cell Polarity / genetics*
  • DNA-Binding Proteins / metabolism
  • Dishevelled Proteins
  • Drosophila / embryology*
  • Drosophila / metabolism
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Early Growth Response Protein 2 / genetics
  • Early Growth Response Protein 2 / metabolism
  • Frizzled Receptors / metabolism
  • Gene Expression Regulation, Developmental
  • LIM Domain Proteins / metabolism
  • Membrane Proteins / metabolism
  • MyoD Protein / genetics
  • MyoD Protein / metabolism
  • Phosphoproteins / metabolism
  • Wings, Animal / embryology*
  • Zebrafish / embryology*
  • Zebrafish / metabolism
  • Zebrafish Proteins / genetics*
  • Zebrafish Proteins / metabolism

Substances

  • Adaptor Protein Complex 1
  • Adaptor Proteins, Signal Transducing
  • Cadherins
  • Carrier Proteins
  • DNA-Binding Proteins
  • Dgo protein, Drosophila
  • Dishevelled Proteins
  • Drosophila Proteins
  • Early Growth Response Protein 2
  • Frizzled Receptors
  • LIM Domain Proteins
  • Membrane Proteins
  • MyoD Protein
  • Phosphoproteins
  • Vang protein, Drosophila
  • Zebrafish Proteins
  • dsh protein, Drosophila
  • pk protein, Drosophila
  • stan protein, Drosophila
  • ADP-Ribosylation Factor 1