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A molecular network for de novo generation of the apical surface and lumen

Nature Cell Biology volume 12, pages 1035–1045 (2010)Cite this article

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Abstract

To form epithelial organs cells must polarize and generate de novo an apical domain and lumen. Epithelial polarization is regulated by polarity complexes that are hypothesized to direct downstream events, such as polarized membrane traffic, although this interconnection is not well understood. We have found that Rab11a regulates apical traffic and lumen formation through the Rab guanine nucleotide exchange factor (GEF), Rabin8, and its target, Rab8a. Rab8a and Rab11a function through the exocyst to target Par3 to the apical surface, and control apical Cdc42 activation through the Cdc42 GEF, Tuba. These components assemble at a transient apical membrane initiation site to form the lumen. This Rab11a-directed network directs Cdc42-dependent apical exocytosis during lumen formation, revealing an interaction between the machineries of vesicular transport and polarization.

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Figure 1: Characterization of lumen initiation in MDCK cysts.
Figure 2: The Rab8 and Rab11 GTPase families direct lumen initiation.
Figure 3: A Rab11–Rabin8–Rab8 complex governs apical transport and single lumenogenesis.
Figure 4: The exocyst and Par3–aPKC regulate lumenogenesis.
Figure 5: Tuba and Cdc42 regulate transport from Rab8a/Rab11a-positive vesicles.
Figure 6: Rab8a/Rab11a regulate Cdc42 during apical transport.
Figure 7: A molecular network for de novo lumen generation.

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Acknowledgements

We thank F. Barr, E. Brown, J. Stow, W. Guo, I. Macara, K. Simons, J. Wilson, T. Weimbs, and A. Zahraoui for gifts of reagents and unpublished data, and the Mostov lab for kind assistance. Supported by a Susan G Komen Foundation Fellowship (D.M.B.), a DOD Breast Cancer Concept Award (A.D.), NIH grants R01DK074398, R01AI25144 and P01AI53194 (K.E.M.), grants of the Human Frontiers Science Program (HFSP-CDA00011/2009), Marie Curie (IRG-209382), MICINN (BFU2008-01916) and (CONSOLIDER CSD2009-00016) to F.M.-B.; and a JAE fellowship (MICINN) to A.E.R.F.

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  1. David M. Bryant and Anirban Datta: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Anatomy, University of California, San Francisco, 94143-2140, CA, USA

    David M. Bryant, Anirban Datta & Keith E. Mostov

  2. Department of Biochemistry and Biophysics, University of California, San Francisco, 94143-2140, CA, USA

    Keith E. Mostov

  3. Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Madrid, 28049, Spain

    Alejo E. Rodríguez-Fraticelli & Fernando Martín-Belmonte

  4. Institute of Biotechnology, Viikinkaari 9, University of Helsinki, Helsinki, FIN-00014, Finland

    Johan Peränen

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Contributions

D.M.B., A.D., A.R.F, F.M.B. and J.P. designed the experiments. D.M.B., A.D., A.R.F. and J.P. did the experimental work. D.M.B. and K.E.M. analysed the experiments. D.M.B. and K.E.M wrote the manuscript.

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Correspondence to Keith E. Mostov.

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Bryant, D., Datta, A., Rodríguez-Fraticelli, A. et al. A molecular network for de novo generation of the apical surface and lumen. Nat Cell Biol 12, 1035–1045 (2010). https://doi.org/10.1038/ncb2106

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