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Yurt, Coracle, Neurexin IV and the Na+,K+-ATPase form a novel group of epithelial polarity proteins

Abstract

The integrity of polarized epithelia is critical for development and human health. Many questions remain concerning the full complement and the function of the proteins that regulate cell polarity1. Here we report that the Drosophila FERM proteins Yurt (Yrt)2 and Coracle (Cora)3 and the membrane proteins Neurexin IV (Nrx-IV)4 and Na+,K+-ATPase5 are a new group of functionally cooperating epithelial polarity proteins. This ‘Yrt/Cora group’ promotes basolateral membrane stability and shows negative regulatory interactions with the apical determinant Crumbs (Crb). Genetic analyses indicate that Nrx-IV and Na+,K+-ATPase act together with Cora in one pathway, whereas Yrt acts in a second redundant pathway. Moreover, we show that the Yrt/Cora group is essential for epithelial polarity during organogenesis but not when epithelial polarity is first established or during terminal differentiation. This property of Yrt/Cora group proteins explains the recovery of polarity in embryos lacking the function of the Lethal giant larvae (Lgl) group of basolateral polarity proteins6,7. We also find that the mammalian Yrt orthologue EPB41L5 (also known as YMO1 and Limulus)8,9,10 is required for lateral membrane formation, indicating a conserved function of Yrt proteins in epithelial polarity.

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Figure 1: Synergistic interactions between Yrt, Na + ,K + -ATPase and Nrx-IV.
Figure 2: Excessive apicalization in cora yrt double mutants and embryos overexpressing Crb.
Figure 3: Mutations in Yrt/Cora-group genes suppress the crb mutant phenotype.
Figure 4: Knockdown of EPB41L5 in MDCK cells compromises lateral membrane formation.

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Acknowledgements

We would like to thank V. Auld, J. Casanova, H. Bellen, M. Hortsch, R. Fehon, M. Bhat, R. Schuh, the Developmental Studies Hybridoma Bank and the Bloomington Drosophila Stock Center for reagents. We thank D. Godt, R. Winklbauer and T. Harris for critical comments on the manuscript, and H. Hong, M. Pellikka and W. Russin for technical assistance. This work was supported by postdoctoral fellowships from the CIHR (to P.L.), a predoctoral fellowship from the Vision Science Research Program, University of Toronto (to S.B.) and by NIH Lung Biology Training Grant 5 (to S.M.P.). Operating support was provided by the CIHR (to U.T. and P.L.), the Foundation Fighting Blindness Canada (to C.J.M.) and the NIH (to G.J.B.).

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Correspondence to Ulrich Tepass.

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Laprise, P., Lau, K., Harris, K. et al. Yurt, Coracle, Neurexin IV and the Na+,K+-ATPase form a novel group of epithelial polarity proteins. Nature 459, 1141–1145 (2009). https://doi.org/10.1038/nature08067

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