Galectin-3 guides intracellular trafficking of some human serotransferrin glycoforms.
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.
From the Section MIG (Microbiology, Immunology, Glycobiology), Department of Laboratory Medicine and.
Michael C
MC
Carlsson
Per
P
Bengtson
Helena
H
Cucak
Hakon
H
Leffler
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism; D002460:Cell Line; D004705:Endocytosis; D005260:Female; D037502:Galectin 3 / Q000378:metabolism*; D006031:Glycosylation; D006801:Humans; D061986:MCF-7 Cells; D008875:Middle Aged; D011134:Polysaccharides / Q000737:chemistry; D011485:Protein Binding; D011487:Protein Conformation; D021381:Protein Transport; D014168:Transferrin / Q000378:metabolism*
D014408:Biomarkers, Tumor; D037502:Galectin 3; D011134:Polysaccharides; D014168:Transferrin
Breast Cancer; Endocytosis; Galectin-3; Glycoforms; Glycosylation; Trafficking; Transferrin