TY - JOUR
T1 - Synaptotagmin-like proteins control the formation of a single apical membrane domain in epithelial cells
AU - Gálvez-Santisteban, Manuel
AU - Rodriguez-Fraticelli, Alejo E.
AU - Bryant, David M.
AU - Vergarajauregui, Silvia
AU - Yasuda, Takao
AU - Bañón-Rodríguez, Inmaculada
AU - Bernascone, Ilenia
AU - Datta, Anirban
AU - Spivak, Natalie
AU - Young, Kitty
AU - Slim, Christiaan L.
AU - Brakeman, Paul R.
AU - Fukuda, Mitsunori
AU - Mostov, Keith E.
AU - Martín-Belmonte, Fernando
N1 - Funding Information:
We thank C. M. Ruiz-Jarabo for comments on the manuscript, and members of the Martin-Belmonte laboratory for discussion. We thank M. ter Beest, J. Peränen, and K. Simons, Max Planck Institute of Molecular Cell Biology and Genetics (MPI-CBG), Dresden, Germany, for generous gifts of reagents, and the Mostov laboratory for kind assistance. This work was supported by grants from the Human Frontiers Science Program (HFSP-CDA 00011/2009), Marie Curie (IRG-209382), MICINN (BFU2008-01916), (BFU2011-22622) and CONSOLIDER (CSD2009-00016) to F.M-B.; by NIH R01DK074398, R01AI25144 and R01DK91530 to K.M., and The March of Dimes Basil O’Connor Starter Research Award to P.R.B. A.E.R-F. is the recipient of a JAE fellowship, from CSIC; M.G-S. is the recipient of a FPI fellowship, from MICINN; and I.B-R. is the recipient of an AECC fellowship. An institutional Grant from the Fundación Ramón Areces to CBMSO is also acknowledged.
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
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U2 - 10.1038/ncb2541
DO - 10.1038/ncb2541
M3 - Article
C2 - 22820376
AN - SCOPUS:84864875660
SN - 1465-7392
VL - 14
SP - 838
EP - 849
JO - Nature Cell Biology
JF - Nature Cell Biology
IS - 8
ER -