Synaptotagmin-like proteins control the formation of a single apical membrane domain in epithelial cells

Gálvez-Santisteban, M. et al. (2012) Synaptotagmin-like proteins control the formation of a single apical membrane domain in epithelial cells. Nature Cell Biology, 14(8), pp. 838-849. (doi: 10.1038/ncb2541) (PMID:22820376) (PMCID:PMC3433678)

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The formation of epithelial tissues requires both the generation of apical-basal polarity and the coordination of this polarity between neighbouring cells to form a central lumen. During de novo lumen formation, vectorial membrane transport contributes to the formation of a singular apical membrane, resulting in the contribution of each cell to only a single lumen. Here, from a functional screen for genes required for three-dimensional epithelial architecture, we identify key roles for synaptotagmin-like proteins 2-a and 4-a (Slp2-a/4-a) in the generation of a single apical surface per cell. Slp2-a localizes to the luminal membrane in a PtdIns(4,5)P(2)-dependent manner, where it targets Rab27-loaded vesicles to initiate a single lumen. Vesicle tethering and fusion is controlled by Slp4-a, in conjunction with Rab27/Rab3/Rab8 and the SNARE syntaxin-3. Together, Slp2-a/4-a coordinate the spatiotemporal organization of vectorial apical transport to ensure that only a single apical surface, and thus the formation of a single lumen, occurs per cell.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Bryant, Dr David
Authors: Gálvez-Santisteban, M., Rodriguez-Fraticelli, A. E., Bryant, D. M., Vergarajauregui, S., Yasuda, T., Bañón-Rodríguez, I., Bernascone, I., Datta, A., Spivak, N., Young, K., Slim, C. L., Brakeman, P. R., Fukuda, M., Mostov, K. E., and Martín-Belmonte, F.
College/School:College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Nature Cell Biology
Publisher:Nature Publishing Group
ISSN (Online):1476-4679
Published Online:22 July 2012

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