Planar cell polarity complex internalization is dependent on Celsr1 cis-dimerization

Planar cell polarity (PCP) coordinates collective cell polarity along a tissue plane through the asymmetric localization of junctional complexes comprised of core transmembrane proteins: Celsr1, Fz6, and Vangl2. Basal cells of embryonic mouse epidermis undergo numerous cell divisions to support the developing tissue while also maintaining tissue-level polarity. To achieve this, junctional PCP complexes are selectively co-internalized by the dividing cell, facilitating the restoration of tissue polarity upon mitotic exit. In Celsr1 Crsh/Crsh epidermis, we identify aberrant mitotic internalization of Celsr1 and Fz6, and a failure to co-internalize Vangl2. Mixed-cell in vitro assays reveal Crsh is deficient in mediating trans- endocytosis of Celsr1 and Vangl2. These defects are rescued through forced dimerization of Crsh, supporting the hypothesis that Celsr1 adhesive interactions stabilized by cis -dimers are required for both PCP establishment and maintenance via trans -endocytosis of PCP complexes. Overall, these findings establish a Celsr1 dimerization-dependent mechanism for control of tissue polarity during cell division.