Editors' ChoiceCell Biology

Ensuring daughter cells get PCP components

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Science Signaling  23 Jun 2015:
Vol. 8, Issue 382, pp. ec170
DOI: 10.1126/scisignal.aac8287

Planar cell polarity (PCP) orients cells within an epithelial sheet and is important for development and maintenance of tissue integrity. PCP is mediated by two distinct PCP complexes at the plasma membrane on opposite sides of the cell. Celsr1 (also known as Flamingo) is present in both PCP complexes and during mitosis is internalized and recruits other PCP components to endosomes. Shrestha et al. found that Celsr1 was phosphorylated specifically during mitosis in cultured mouse keratinocytes and colocalized with the mitotic serine-threonine kinase Polo-like kinase 1 (Plk1) at endosomes from prophase until early cytokinesis in mouse skin epithelia explants. A dileucine motif in the cytoplasmic portion of Celsr1 mediates recruitment of the protein into endosomes, and the region near this motif was phosphorylated in keratinocytes during mitosis in a Plk1-dependent manner. In vitro, Plk1 phosphorylated several serine and threonine residues near the endocytic motif of Celsr1. Pharmacologically inhibiting Plk1 activity or expressing a form of Celsr1 in which the threonine and serine residues phosphorylated by Plk1 were mutated to alanines reduced endocytosis of Celsr1 during mitosis of keratinocytes. When expressed in keratinocytes, a form of Celsr1 with phosphomimetic mutations in the region with the endocytic motif was present in endosomes during interphase and was internalized during mitosis even when Plk1 was inhibited. Plk1 contains a polo-box domain (PBD) that binds to PBD-binding motifs in target proteins. A PBD-binding motif in the cytoplasmic tail of Celsr1 was required for Celsr1 to interact with Plk1 and for Celsr1 internalization during mitosis in keratinocytes. Thus, Plk1 drives internalization of Ceslr1 during mitosis, which in turn recruits other PCP components to the endosome for redistribution to daughter cells. Commentary by Sedzinski and Wallingford highlights the implications of these findings for understanding the links between cell cycle and cell polarity.

R. Shrestha, K. A. Little, J. V. Tamayo, W. Li, D. H. Perlman, D. Devenport, Mitotic control of planar cell polarity by polo-like kinase 1. Dev. Cell. 33, 522–534 (2015). [PubMed]

J. Sedzinski, J. Wallingford, Planar pol(o)arity. Dev. Cell. 33, 494–495 (2015). [PubMed]

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