Mitotic Control of Planar Cell Polarity by Polo-like Kinase 1

• Published in: Developmental cell Vol. 33; no. 5; pp. 522 - 534
• Main Authors: Shrestha, Rezma, Little, Katherine A., Tamayo, Joel V., Li, Wenyang, Perlman, David H., Devenport, Danelle
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.06.2015
• Subjects: Amino Acid Motifs; Amino Acid Sequence; Animals; Cell Cycle Proteins - metabolism; Cell Polarity - physiology; Endocytosis - physiology; Endosomes - metabolism; Fluorescent Antibody Technique; HeLa Cells; Humans; Interphase; Keratinocytes - cytology; Keratinocytes - metabolism; Mice; Mitosis - physiology; Molecular Sequence Data; Phosphorylation; Polo-Like Kinase 1; Protein Binding; Protein Serine-Threonine Kinases - metabolism; Proto-Oncogene Proteins - metabolism; Receptors, G-Protein-Coupled - metabolism; Sequence Homology, Amino Acid; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
• ISSN: 1534-5807; 1878-1551
• DOI: 10.1016/j.devcel.2015.03.024

During cell division, polarized epithelial cells employ mechanisms to preserve cell polarity and tissue integrity. In dividing cells of the mammalian skin, planar cell polarity (PCP) is maintained through the bulk internalization, equal segregation, and polarized recycling of cortical PCP proteins. The dramatic redistribution of PCP proteins coincides precisely with cell-cycle progression, but the mechanisms coordinating PCP and mitosis are unknown. Here we identify Plk1 as a master regulator of PCP dynamics during mitosis. Plk1 interacts with core PCP component Celsr1 via a conserved polo-box domain (PBD)-binding motif, localizes to mitotic endosomes, and directly phosphorylates Celsr1. Plk1-dependent phosphorylation activates the endocytic motif specifically during mitosis, allowing bulk recruitment of Celsr1 into endosomes. Inhibiting Plk1 activity blocks PCP internalization and perturbs PCP asymmetry. Mimicking dileucine motif phosphorylation is sufficient to drive Celsr1 internalization during interphase. Thus, Plk1-mediated phosphorylation of Celsr1 ensures that PCP redistribution is precisely coordinated with mitotic entry. [Display omitted] •Plk1 localizes to mitotic endosomes and phosphorylates Celsr1’s endocytic motif•Plk1-dependent phosphorylation is necessary for Celsr1 mitotic endocytosis•Celsr1 recruits Plk1 via a PBD-binding motif required for internalization•Phosphomimetic mutations can uncouple Celsr1 internalization from mitosis In polarized epithelial cells, planar cell polarity (PCP) proteins are internalized during mitosis and then redistributed with cell-cycle progression. Shrestha et al. now show that the mitotic regulator Polo-like kinase 1 (Plk1) coordinates this process via phosphorylation of the PCP protein Celsr1, which promotes Celsr1 endocytosis during mitosis.