Oligomerization of the FERM-FA protein Yurt controls epithelial cell polarity

• Published in: The Journal of cell biology Vol. 217; no. 11; pp. 3853 - 3862
• Main Authors: Gamblin, Clémence L, Parent-Prévost, Frédérique, Jacquet, Kévin, Biehler, Cornélia, Jetté, Alexandra, Laprise, Patrick
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 05.11.2018
• Subjects: Cells; Epithelial cells; Ezrin; Fruit flies; Kinases; Mesenchyme; Metastases; Metastasis; Moesin; Molecular biology; Molecular modelling; Oligomerization; Polarity; Protein structure; Proteins; Quaternary structure; Radixin
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201803099

Yurt (Yrt) and its mammalian orthologue EPB41L5 limit apical membrane growth in polarized epithelia. EPB41L5 also supports epithelial-mesenchymal transition and metastasis. Yrt and EPB41L5 contain a four-point-one, ezrin, radixin, and moesin (FERM) domain and a FERM-adjacent (FA) domain. The former contributes to the quaternary structure of 50 human proteins, whereas the latter defines a subfamily of 14 human FERM proteins and fulfills unknown roles. In this study, we show that both Yrt and EPB41L5 oligomerize. Our data also establish that the FERM-FA unit forms an oligomeric interface and that multimerization of Yrt is crucial for its function in epithelial cell polarity regulation. Finally, we demonstrate that aPKC destabilizes the Yrt oligomer to repress its functions, thereby revealing a mechanism through which this kinase supports apical domain formation. Overall, our study highlights a conserved biochemical property of fly and human Yrt proteins, describes a novel function of the FA domain, and further characterizes the molecular mechanisms sustaining epithelial cell polarity.