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Endocytic control of epithelial polarity and proliferation in Drosophila

Nature Cell Biology volume 7, pages 1232–1239 (2005)Cite this article

An Erratum to this article was published on 02 December 2005

Abstract

Intracellular protein transport is a key factor in epithelial cell polarity. Here we report that mutations in two core components of the vesicle trafficking machinery — a syntaxin and a Rab protein — cause an expansion of the apical membrane domain of Drosophila melanogaster epithelia; this polarity defect is coupled with overproliferation to form neoplastic tumours. Surprisingly, these proteins are associated with the endocytic, and not the exocytic, pathway. The syntaxin Avalanche (Avl) localizes to early endosomes, and loss of avl results in the cellular accumulation of specific membrane proteins, including the Notch signalling receptor and the polarity determinant Crumbs (Crb). Protein accumulation results from a failure in endosomal entry and progression towards lysosomal degradation; these and other avl phenotypes are also detected in Rab5 null mutant cells. Overexpression of Crb alone is sufficient to induce overproliferation of wild-type imaginal tissue, suggesting that polarity alterations in avl and Rab5 mutants directly contribute to tumour formation. Our findings reveal a critical and specific role for endocytic traffic in the control of both apico-basal polarity and cell proliferation.

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Figure 1: avl mutations disrupt epithelial polarity and proliferation control.
Figure 2: avl encodes a Drosophila syntaxin.
Figure 3: Avl is localized to endocytic vesicles.
Figure 4: avl tissue is defective in endocytic trafficking and accumulates specific membrane proteins.
Figure 5: Notch trafficking in the endocytic mutants Rab5 and hrs.

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Acknowledgements

We thank C. Hsu for excellent technical assistance, S. Horne-Badovinac for providing avl3 and avl4 and the entire staff of the Bilder lab for thoughtful input. Our thanks also go to I. Hariharan, G. Garriga, and S. Martin for comments on the manuscript. We are particularly grateful to M. Gonzalez-Gaitan, H. Bellen, S. Campuzano, R. Cohen, H. Kramer, S. Bray and N. Azpiazu for kindly providing reagents. We apologize to those whose work could only be cited in review articles. This work was supported by National Institutes of Health grant GM 068675-01, a Burroughs-Wellcome Fund career development award, and a Searle Scholars award to D.B.

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  1. Department of Molecular and Cell Biology, University of California-Berkeley, 142 LSA #3200, Berkeley, 94720-3200, CA, USA

    Han Lu & David Bilder

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  1. Han Lu
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  2. David Bilder
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Correspondence to David Bilder.

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Lu, H., Bilder, D. Endocytic control of epithelial polarity and proliferation in Drosophila. Nat Cell Biol 7, 1232–1239 (2005). https://doi.org/10.1038/ncb1324

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