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

Manuel Gálvez-Santisteban, Alejo E. Rodriguez-Fraticelli, David M. Bryant, Silvia Vergarajauregui, Takao Yasuda, Inmaculada Bañón-Rodríguez, Ilenia Bernascone, Anirban Datta, Natalie Spivak, Kitty Young, Christiaan L. Slim, Paul R. Brakeman, Mitsunori Fukuda, Keith E. Mostov, Fernando Martín-Belmonte

    Research output: Contribution to journalArticlepeer-review

    100 Citations (Scopus)


    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.

    Original languageEnglish
    Pages (from-to)838-849
    Number of pages12
    JournalNature cell biology
    Issue number8
    Publication statusPublished - 2012 Aug

    ASJC Scopus subject areas

    • Cell Biology


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