Galectin-3 guides intracellular trafficking of some human serotransferrin glycoforms

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Galectin-3 guides intracellular trafficking of some human serotransferrin glycoforms. / Carlsson, Michael; Bengtson, Per; Cucak, Helena; Leffler, Hakon.

In: Journal of Biological Chemistry, Vol. 288, No. 39, 2013, p. 28398-28408.

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T1 - Galectin-3 guides intracellular trafficking of some human serotransferrin glycoforms

AU - Carlsson, Michael

AU - Bengtson, Per

AU - Cucak, Helena

AU - Leffler, Hakon

PY - 2013

Y1 - 2013

N2 - 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 degree of iron loading, but not other forms of heterogeneity.

AB - 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 degree of iron loading, but not other forms of heterogeneity.

KW - Galectin

KW - transferrin

KW - glycoforms

KW - trafficking

KW - endocytosis

U2 - 10.1074/jbc.M113.487793

DO - 10.1074/jbc.M113.487793

M3 - Article

C2 - 23926108

VL - 288

SP - 28398

EP - 28408

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 1083-351X

IS - 39

ER -