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Nat Cell Biol. 2015 Mar;17(3):241-50. doi: 10.1038/ncb3106. Epub 2015 Feb 23.

Developmental regulation of apical endocytosis controls epithelial patterning in vertebrate tubular organs.

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Department of Development and Differentiation, Centro de Biología Molecular 'Severo Ochoa', CSIC-UAM, Madrid 28049, Spain.
Department of Cell Biology, Duke University, Durham, North Carolina 27710, USA.
Department of Subcellular Structure and Cellular Dynamics, UMR144, Institut Curie, Paris 75005, France.
Department of Immunology and Cell Biology, Centro de Biología Molecular 'Severo Ochoa', CSIC-UAM, Madrid 28049, Spain.
Electron Microscopy Core, Centro de Biología Molecular 'Severo Ochoa', CSIC-UAM, Madrid 28049, Spain.


Epithelial organs develop through tightly coordinated events of cell proliferation and differentiation in which endocytosis plays a major role. Despite recent advances, how endocytosis regulates the development of vertebrate organs is still unknown. Here we describe a mechanism that facilitates the apical availability of endosomal SNARE receptors for epithelial morphogenesis through the developmental upregulation of plasmolipin (pllp) in a highly endocytic segment of the zebrafish posterior midgut. The protein PLLP (Pllp in fish) recruits the clathrin adaptor EpsinR to sort the SNARE machinery of the endolysosomal pathway into the subapical compartment, which is a switch for polarized endocytosis. Furthermore, PLLP expression induces apical Crumbs internalization and the activation of the Notch signalling pathway, both crucial steps in the acquisition of cell polarity and differentiation of epithelial cells. We thus postulate that differential apical endosomal SNARE sorting is a mechanism that regulates epithelial patterning.

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