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

• Published in: Nature cell biology Vol. 17; no. 3; pp. 241 - 250
• Main Authors: Rodríguez-Fraticelli, Alejo E., Bagwell, Jennifer, Bosch-Fortea, Minerva, Boncompain, Gaelle, Reglero-Real, Natalia, García-León, Maria J., Andrés, Germán, Toribio, Maria L., Alonso, Miguel A., Millán, Jaime, Perez, Franck, Bagnat, Michel, Martín-Belmonte, Fernando
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.03.2015; Nature Publishing Group
• Subjects: 13/1; 13/109; 13/89; 13/95; 14/19; 14/28; 14/34; 14/69; 38; 38/39; 38/77; 38/88; 42; 45; 59; 631/136; 631/80/313/1461; 631/80/313/2104; 631/80/85/2361; 64/116; 64/60; 82/51; 96; 96/106; Adaptor Proteins, Vesicular Transport - genetics; Adaptor Proteins, Vesicular Transport - metabolism; Animals; Artificial chromosomes; Biology; Cancer Research; Cell Biology; Cell Differentiation; Cell Line; Cell Polarity; Cell Proliferation; Cell research; Cellular proteins; Danio rerio; Developmental Biology; Embryo, Nonmammalian; Endocytosis; Endosomes - metabolism; Endosomes - ultrastructure; Epithelial Cells - metabolism; Epithelial Cells - ultrastructure; Epithelium - metabolism; Epithelium - ultrastructure; Gene Expression Regulation, Developmental; Genes; Kidney Tubules - metabolism; Kidney Tubules - ultrastructure; Life Sciences; Lysosomes - metabolism; Lysosomes - ultrastructure; Mice; Microscopy; Morphogenesis; Myelin and Lymphocyte-Associated Proteolipid Proteins - genetics; Myelin and Lymphocyte-Associated Proteolipid Proteins - metabolism; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Properties; Proteins; Receptors, Notch - genetics; Receptors, Notch - metabolism; Signal Transduction; SNARE Proteins - genetics; SNARE Proteins - metabolism; Stem Cells; Vertebrates; Zebrafish; Spain
• ISSN: 1465-7392; 1476-4679
• DOI: 10.1038/ncb3106

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. Bagnat, Martín-Belmonte and colleagues reveal that plasmolipin (PLLP) is upregulated in the zebrafish midgut during development and controls epithelial patterning by promoting polarized endocytosis.