TY - JOUR
T1 - Mitotic Control of Planar Cell Polarity by Polo-like Kinase 1
AU - Shrestha, Rezma
AU - Little, Katherine A.
AU - Tamayo, Joel V.
AU - Li, Wenyang
AU - Perlman, David H.
AU - Devenport, Danelle
N1 - Funding Information:
We thank Kyung S. Lee for the Plk1-GFP constructs, Henry Shwe for MS data acquisition, Alexei Korennykh and lab members for generous assistance with in vitro kinase assays, and Gary Laevsky for technical assistance with imaging. We are grateful to Rebecca Burdine and Paul Schedl for helpful discussions and to D.D. lab members for discussions and feedback, especially Bryan Heck and Wen Yih Aw for help with image quantification. Work was supported by NIH/NIAMS Pathway to Independence Award R00AR057501.
Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/6/8
Y1 - 2015/6/8
N2 - 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 ofCelsr1 into endosomes. Inhibiting Plk1 activity blocks PCP internalization and perturbs PCP asymmetry. Mimicking dileucine motif phosphorylation issufficient to drive Celsr1 internalization during interphase. Thus, Plk1-mediated phosphorylation of Celsr1 ensures that PCP redistribution is precisely coordinated with mitotic entry.
AB - 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 ofCelsr1 into endosomes. Inhibiting Plk1 activity blocks PCP internalization and perturbs PCP asymmetry. Mimicking dileucine motif phosphorylation issufficient to drive Celsr1 internalization during interphase. Thus, Plk1-mediated phosphorylation of Celsr1 ensures that PCP redistribution is precisely coordinated with mitotic entry.
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U2 - 10.1016/j.devcel.2015.03.024
DO - 10.1016/j.devcel.2015.03.024
M3 - Article
C2 - 26004507
AN - SCOPUS:84930572606
SN - 1534-5807
VL - 33
SP - 522
EP - 534
JO - Developmental cell
JF - Developmental cell
IS - 5
ER -