Cell cycle control of the endocytic recycling of planar cell polarity protein Celsr1 during late phases of mitosis

Abstract

Specific mechanisms and regulation are needed to maintain planar cell polarity (PCP), the coordinated local and global polarization of core protein components along the epithelial plane, during mitosis when cells undergo drastic morphological change. PCP components at the cell surface internalize into endosomes at the start of mitosis and are retained until mitotic exit, when they equally segregate to daughter cells and repolarize at the plasma membrane. Plk1 phosphorylates the C-terminal endocytic motif of PCP component Celsr1 to tightly coordinate mitotic onset with the bulk internalization of Celsr1 into clathrin-coated endosomes. However, after internalization, little is known about the mechanism of retention, endocytic machinery, and cell cycle control required for Celsr1 recycling during mitotic exit. We show here that recycling to the plasma membrane is tightly coordinated with cell cycle progression by the Cdk1 inactivation event at the metaphase/anaphase transition and that Plk1 kinase activity is essential for retention of endosomes during mitotic progression. We also show co-localization of Celsr1-containing endosomes with two endocytic machinery components, the Vps35 retromer subunit and Snx27 cargo adaptor, as well as a functional role for the Vps35 retromer subunit in directing Celsr1 endosomes to the plasma membrane. These characterizations reveal further how PCP is consistently maintained with high fidelity across cell generations.