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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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Barr, E. Brown, J. Stow, W. Guo, I. Macara, K. Simons, J. Wilson, T. Weimbs, and A. Zahraoui for gifts of reagents and unpublished data, and the Mostov lab for kind assistance.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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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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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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DOI: https://doi.org/10.1038/ncb2106
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