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Localization of apical epithelial determinants by the basolateral PDZ protein Scribble

Nature volume 403, pages 676–680 (2000)Cite this article

Abstract

The generation of membrane domains with distinct protein constituents is a hallmark of cell polarization. In epithelia, segregation of membrane proteins into apical and basolateral compartments is critical for cell morphology, tissue physiology and cell signalling. Drosophila proteins that confer apical membrane identity have been found1,2, but the mechanisms that restrict these determinants to the apical cell surface are unknown. Here we show that a laterally localized protein is required for the apical confinement of polarity determinants. Mutations in Drosophila scribble (scrib), which encodes a multi-PDZ (PSD-95, Discs-large and ZO-1) and leucine-rich-repeat protein, cause aberrant cell shapes and loss of the monolayer organization of embryonic epithelia. Scrib is localized to the epithelial septate junction, the analogue of the vertebrate tight junction3, at the boundary of the apical and basolateral cell surfaces. Loss of scrib function results in the misdistribution of apical proteins and adherens junctions to the basolateral cell surface, but basolateral protein localization remains intact. These phenotypes can be accounted for by mislocalization of the apical determinant Crumbs. Our results show that the lateral domain of epithelia, particularly the septate junction, functions in restricting apical membrane identity and correctly placing adherens junctions.

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Figure 1: scrib mutations cause disorganization of epithelia.
Figure 2: Cloning of scrib.
Figure 3: Expression and localization of Scrib.
Figure 4: scrib embryos mislocalize apical proteins.

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Acknowledgements

We would like to thank E. Knust, M. Bhat, D. Kiehart, R. Fehon, D. Cavener, H. Oda and K. Anderson for providing antibodies and fly stocks. We are indebted to Min Li for excellent technical assistance and B. Mathey-Prevot, M. Petitt, and I. The for comments on the manuscript. D.B. is an American Cancer Society Fellow. N.P. is an Investigator of the Howard Hughes Medical Institute.

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  1. Department of Genetics,

    David Bilder & Norbert Perrimon

  2. Howard Hughes Medical Institute, Harvard Medical School, 200 Longwood Avenue, Boston, 02115, Massachussetts, USA

    Norbert Perrimon

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  1. David Bilder
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Correspondence to David Bilder.

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Bilder, D., Perrimon, N. Localization of apical epithelial determinants by the basolateral PDZ protein Scribble. Nature 403, 676–680 (2000). https://doi.org/10.1038/35001108

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