Mitotic internalization of planar cell polarity proteins preserves tissue polarity

Abstract

Planar cell polarity (PCP) is the collective polarization of cells along the epithelial plane, a process best understood in the terminally differentiated Drosophila wing. Proliferative tissues such as mammalian skin also show PCP, but the mechanisms that preserve tissue polarity during proliferation are not understood. During mitosis, asymmetrically distributed PCP components risk mislocalization or unequal inheritance, which could have profound consequences for the long-range propagation of polarity. Here, we show that when mouse epidermal basal progenitors divide PCP components are selectively internalized into endosomes, which are inherited equally by daughter cells. Following mitosis, PCP proteins are recycled to the cell surface, where asymmetry is re-established by a process reliant on neighbouring PCP. A cytoplasmic dileucine motif governs mitotic internalization of atypical cadherin Celsr1, which recruits Vang2 and Fzd6 to endosomes. Moreover, embryos transgenic for a Celsr1 that cannot mitotically internalize exhibit perturbed hair-follicle angling, a hallmark of defective PCP. This underscores the physiological relevance and importance of this mechanism for regulating polarity during cell division. Planar cell polarity (PCP) directs the orientation of mammalian epithelial cells in the skin but it is unclear how polarity is preserved during division. A dileucine motif in the atypical cadherin Celsr1 is shown to trigger the endocytosis of PCP components in mitosis to ensure that they are distributed equally to daughter cells and recycled back to the plasma membrane after division.

Cite this article

Devenport, D., Oristian, D., Heller, E. et al. Mitotic internalization of planar cell polarity proteins preserves tissue polarity. Nat Cell Biol 13, 893–902 (2011). https://doi.org/10.1038/ncb2284

View full text

>> Full Text:   Mitotic internalization of planar cell polarity proteins preserves tissue polarity