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

Patrick Laprise; Kimberly M. Lau; Kathryn P. Harris; Nancy F. Silva-Gagliardi; Sarah M. Paul; Slobodan Beronja; Greg J. Beitel; C. Jane McGlade; Ulrich Tepass

doi:10.1038/nature08067

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

Patrick Laprise, Kimberly M. Lau, Kathryn P. Harris, Nancy F. Silva-Gagliardi, Sarah M. Paul, Slobodan Beronja, Greg J. Beitel, C. Jane McGlade, Ulrich Tepass^*

^*Corresponding author for this work

Molecular Biosciences

Research output: Contribution to journal › Article › peer-review

135 Scopus citations

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 lack-ing the function of the Lethal giant larvae (Lgl) group of baso-lateral polarity proteins^6,7. We also find that the mammalian Yrt orthologue EPB41L5 (also known as YMO1 and Limulus)^8-10 is required for lateral membrane formation, indicating a conserved function of Yrt proteins in epithelial polarity.

Original language	English (US)
Pages (from-to)	1141-1145
Number of pages	5
Journal	Nature
Volume	459
Issue number	7250
DOIs	https://doi.org/10.1038/nature08067
State	Published - Jun 25 2009

Funding

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.).

ASJC Scopus subject areas

General

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Cite this

@article{55384a3d424e4c9988dcdbb88b665e69,

title = "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 lack-ing the function of the Lethal giant larvae (Lgl) group of baso-lateral polarity proteins6,7. We also find that the mammalian Yrt orthologue EPB41L5 (also known as YMO1 and Limulus)8-10 is required for lateral membrane formation, indicating a conserved function of Yrt proteins in epithelial polarity.",

author = "Patrick Laprise and Lau, {Kimberly M.} and Harris, {Kathryn P.} and Silva-Gagliardi, {Nancy F.} and Paul, {Sarah M.} and Slobodan Beronja and Beitel, {Greg J.} and McGlade, {C. Jane} and Ulrich Tepass",

note = "Funding Information: 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.).",

year = "2009",

month = jun,

day = "25",

doi = "10.1038/nature08067",

language = "English (US)",

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pages = "1141--1145",

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T1 - Yurt, Coracle, Neurexin IV and the Na+, K+-ATPase form a novel group of epithelial polarity proteins

AU - Laprise, Patrick

AU - Lau, Kimberly M.

AU - Harris, Kathryn P.

AU - Silva-Gagliardi, Nancy F.

AU - Paul, Sarah M.

AU - Beronja, Slobodan

AU - Beitel, Greg J.

AU - McGlade, C. Jane

AU - Tepass, Ulrich

N1 - Funding Information: 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.).

PY - 2009/6/25

Y1 - 2009/6/25

N2 - 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 lack-ing the function of the Lethal giant larvae (Lgl) group of baso-lateral polarity proteins6,7. We also find that the mammalian Yrt orthologue EPB41L5 (also known as YMO1 and Limulus)8-10 is required for lateral membrane formation, indicating a conserved function of Yrt proteins in epithelial polarity.

AB - 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 lack-ing the function of the Lethal giant larvae (Lgl) group of baso-lateral polarity proteins6,7. We also find that the mammalian Yrt orthologue EPB41L5 (also known as YMO1 and Limulus)8-10 is required for lateral membrane formation, indicating a conserved function of Yrt proteins in epithelial polarity.

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