Galectin-3 guides intracellular trafficking of some human serotransferrin glycoforms

J Biol Chem. 2013 Sep 27;288(39):28398-408. doi: 10.1074/jbc.M113.487793. Epub 2013 Aug 7.


Transferrin internalization via clathrin-mediated endocytosis and subsequent recycling after iron delivery has been extensively studied. Here we demonstrate a previously unrecognized parameter regulating this recycling, the binding of galectin-3 to particular glycoforms of transferrin. Two fractions of transferrin, separated by affinity chromatography based on their binding or not to galectin-3, are targeted to kinetically different endocytic pathways in HFL-1 cells expressing galectin-3 but not in SKBR3 cells lacking galectin-3; the SKBR3 cells, however, can acquire the ability to target these transferrin glycoforms differently after preloading with exogenously added galectin-3. In all, this study provides the first evidence of a functional role for transferrin glycans, in intracellular trafficking after uptake. Moreover, the galectin-3-bound glycoform increased in cancer, suggesting a pathophysiological regulation. These are novel aspects of transferrin cell biology, which has previously considered only a degree of iron loading, but not other forms of heterogeneity.

Keywords: Breast Cancer; Endocytosis; Galectin-3; Glycoforms; Glycosylation; Trafficking; Transferrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / metabolism
  • Cell Line
  • Endocytosis*
  • Female
  • Galectin 3 / metabolism*
  • Glycosylation
  • Humans
  • MCF-7 Cells
  • Middle Aged
  • Polysaccharides / chemistry
  • Protein Binding
  • Protein Conformation
  • Protein Transport
  • Transferrin / metabolism*


  • Biomarkers, Tumor
  • Galectin 3
  • Polysaccharides
  • Transferrin