Epithelial septate junction assembly relies on melanotransferrin iron binding and endocytosis in Drosophila

Nat Cell Biol. 2010 Nov;12(11):1071-7. doi: 10.1038/ncb2111. Epub 2010 Oct 10.


Iron is an essential element in many biological processes. In vertebrates, serum transferrin is the major supplier of iron to tissues, but the function of additional transferrin-like proteins remains poorly understood. Melanotransferrin (MTf) is a phylogenetically conserved, iron-binding epithelial protein. Elevated MTf levels have been implicated in melanoma pathogenesis. Here, we present a functional analysis of MTf in Drosophila melanogaster. Similarly to its human homologue, Drosophila MTf is a lipid-modified, iron-binding protein attached to epithelial cell membranes, and is a component of the septate junctions that form the paracellular permeability barrier in epithelial tissues. We demonstrate that septate junction assembly during epithelial maturation relies on endocytosis and apicolateral recycling of iron-bound MTf. Mouse MTf complements the defects of Drosophila MTf mutants. Drosophila provides the first genetic model for the functional dissection of MTf in epithelial junction assembly and morphogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / cytology*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Endocytosis*
  • Epithelium / metabolism*
  • GPI-Linked Proteins / genetics
  • GPI-Linked Proteins / metabolism
  • Glycosylphosphatidylinositols / metabolism
  • Intercellular Junctions / metabolism*
  • Iron / metabolism*
  • Metalloproteins / genetics
  • Metalloproteins / metabolism*
  • Mice
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Protein Binding


  • Drosophila Proteins
  • GPI-Linked Proteins
  • Glycosylphosphatidylinositols
  • Meltf protein, mouse
  • Metalloproteins
  • Neoplasm Proteins
  • melanotransferrin, Drosophila
  • Iron