Elucidating the Adhesive Mechanism of the Atypical Cadherin CELSR1 Involved in Planar Cell Polarity

Abstract

In multicellular organisms, planar cell polarity (PCP) ensures the proper development of diverse organs during embryogenesis. PCP is characterized by the asymmetric distribution of two groups of transmembrane protein complexes on the apical region of the cell: Cadherin EGF like Laminin G Seven pass type G protein Receptor 1 (CELSR1) and Frizzled (Fzd3/6) on one side; CELSR1 and Vang like- (Vang2) on the opposite side. Among these proteins, CELSR1, an atypical cadherin with nine extracellular cadherin (EC) repeats, modulates the transmission of polarization information across the apical plane through homophilic interactions between adjacent cells. We use a combination of biophysical and biochemical techniques such as bead aggregation assays and multi angle light scattering to explore the adhesive function of CELSR1. While CELSR1 has additional extracellular domains such as EGF, LamG and EGF_Lam following the nine EC repeats, we show that adhesion can be mediated by the first few N-terminal EC repeats rather than the whole extracellular domain of the protein. These results illuminate the adhesive mechanism of CELSR1 important for PCP.