title: Developmental regulation of apical endocytosis controls epithelial patterning in vertebrate tubular organs.
abstract: 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.
authors.affiliation: Department of Development and Differentiation, Centro de Biología Molecular 'Severo Ochoa', CSIC-UAM, Madrid 28049, Spain.
authors.forename: Alejo E
authors.initials: AE
authors.lastname: Rodríguez-Fraticelli
authors.affiliation: Department of Cell Biology, Duke University, Durham, North Carolina 27710, USA.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Bagwell
authors.affiliation: Department of Development and Differentiation, Centro de Biología Molecular 'Severo Ochoa', CSIC-UAM, Madrid 28049, Spain.
authors.forename: Minerva
authors.initials: M
authors.lastname: Bosch-Fortea
authors.affiliation: Department of Subcellular Structure and Cellular Dynamics, UMR144, Institut Curie, Paris 75005, France.
authors.forename: Gaelle
authors.initials: G
authors.lastname: Boncompain
authors.affiliation: Department of Immunology and Cell Biology, Centro de Biología Molecular 'Severo Ochoa', CSIC-UAM, Madrid 28049, Spain.
authors.forename: Natalia
authors.initials: N
authors.lastname: Reglero-Real
authors.affiliation: Department of Immunology and Cell Biology, Centro de Biología Molecular 'Severo Ochoa', CSIC-UAM, Madrid 28049, Spain.
authors.forename: Maria J
authors.initials: MJ
authors.lastname: García-León
authors.affiliation: Electron Microscopy Core, Centro de Biología Molecular 'Severo Ochoa', CSIC-UAM, Madrid 28049, Spain.
authors.forename: Germán
authors.initials: G
authors.lastname: Andrés
authors.affiliation: Department of Immunology and Cell Biology, Centro de Biología Molecular 'Severo Ochoa', CSIC-UAM, Madrid 28049, Spain.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Toribio
authors.affiliation: Department of Immunology and Cell Biology, Centro de Biología Molecular 'Severo Ochoa', CSIC-UAM, Madrid 28049, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Alonso
authors.affiliation: Department of Immunology and Cell Biology, Centro de Biología Molecular 'Severo Ochoa', CSIC-UAM, Madrid 28049, Spain.
authors.forename: Jaime
authors.initials: J
authors.lastname: Millán
authors.affiliation: Department of Subcellular Structure and Cellular Dynamics, UMR144, Institut Curie, Paris 75005, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Perez
authors.affiliation: Department of Cell Biology, Duke University, Durham, North Carolina 27710, USA.
authors.forename: Michel
authors.initials: M
authors.lastname: Bagnat
authors.affiliation: Department of Development and Differentiation, Centro de Biología Molecular 'Severo Ochoa', CSIC-UAM, Madrid 28049, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Martín-Belmonte
mesh_terms: D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D016764:Cell Polarity; D049109:Cell Proliferation; D004625:Embryo, Nonmammalian; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism* / Q000648:ultrastructure; D004847:Epithelial Cells / Q000378:metabolism* / Q000648:ultrastructure; D004848:Epithelium / Q000378:metabolism* / Q000648:ultrastructure; D018507:Gene Expression Regulation, Developmental; D007684:Kidney Tubules / Q000378:metabolism / Q000648:ultrastructure; D008247:Lysosomes / Q000378:metabolism* / Q000648:ultrastructure; D051379:Mice; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015027:Zebrafish
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D009419:Nerve Tissue Proteins; D051880:Receptors, Notch; D050600:SNARE Proteins