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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Cell Differentiation
  • Cell Line
  • Cell Polarity
  • Cell Proliferation
  • Embryo, Nonmammalian
  • Endocytosis
  • Endosomes / metabolism*
  • Endosomes / ultrastructure
  • Epithelial Cells / metabolism*
  • Epithelial Cells / ultrastructure
  • Epithelium / metabolism*
  • Epithelium / ultrastructure
  • Gene Expression Regulation, Developmental*
  • Kidney Tubules / metabolism
  • Kidney Tubules / ultrastructure
  • Lysosomes / metabolism*
  • Lysosomes / ultrastructure
  • Mice
  • Myelin and Lymphocyte-Associated Proteolipid Proteins / genetics
  • Myelin and Lymphocyte-Associated Proteolipid Proteins / metabolism
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism
  • SNARE Proteins / genetics
  • SNARE Proteins / metabolism
  • Signal Transduction
  • Zebrafish

Substances

  • Adaptor Proteins, Vesicular Transport
  • Myelin and Lymphocyte-Associated Proteolipid Proteins
  • Nerve Tissue Proteins
  • Receptors, Notch
  • SNARE Proteins