Trans-endocytosis of Planar Cell Polarity Complexes during Cell Division

Curr Biol. 2017 Dec 4;27(23):3725-3733.e4. doi: 10.1016/j.cub.2017.10.053. Epub 2017 Nov 22.


To coordinate epithelial architecture with proliferation, cell polarity proteins undergo extensive remodeling during cell division [1-3]. A dramatic example of polarity remodeling occurs in proliferative basal cells of mammalian epidermis whereupon cell division, transmembrane planar cell polarity (PCP) proteins are removed from the cell surface via bulk endocytosis [4]. PCP proteins form intercellular complexes, linked by Celsr1-mediated homophilic adhesion, that coordinate polarity non-autonomously between cells [5, 6]. Thus, the mitotic reorganization of PCP proteins must alter not only proteins intrinsic to the dividing cell but also their interacting partners on neighboring cells. Here, we show that intercellular Celsr1 complexes that connect dividing cells with their neighbors remain intact during mitotic internalization, resulting in an uptake of Celsr1 protein from interphase neighbors. Trans-internalized Celsr1 carries with it additional core PCP proteins, including the posteriorly enriched Fz6 and anteriorly enriched Vangl2. Cadherin-mediated homophilic adhesion is necessary for trans-endocytosis, and adhesive junctional PCP complexes appear to be destined for degradation upon internalization. Surprisingly, whereas Fz6 and Vangl2 both internalize in trans, Vangl2 proteins intrinsic to the dividing cell remain associated with the plasma membrane. Persistent Vangl2 stabilizes Celsr1 and impedes its internalization, suggesting that dissociation of Vangl2 from Celsr1 is a prerequisite for Celsr1 endocytosis. These results demonstrate an unexpected transfer of PCP complexes between neighbors and suggest that the Vangl2 population that persists at the membrane during cell division could serve as an internal cue for establishing PCP in new daughter cells.

Keywords: Celsr1; Fz6; Vangl2; endocytosis; epidermis; mitosis; planar cell polarity; skin; trans-endocytosis.

MeSH terms

  • Animals
  • Cell Division*
  • Cell Line
  • Cell Polarity*
  • Endocytosis*
  • Female
  • Keratinocytes
  • Male
  • Mice
  • Mice, Transgenic
  • Receptors, G-Protein-Coupled / metabolism


  • Receptors, G-Protein-Coupled