pH‐Dependent Recycling of Galectin‐3 at the Apical Membrane of Epithelial Cells

Abstract

The β-galactoside binding protein galectin-3 is highly expressed in a variety of epithelial cell lines. Polarized MDCK cells secrete this lectin predominantly into the apical medium by non-classical secretion. Once within the apical extracellular milieu, galectin-3 can reenter the cell followed by passage through endosomal organelles and modulate apical protein sorting. Here, we could show that galectin-3 is internalized by non-clathrin mediated endocytosis. Within endosomal organelles this pool associates with newly synthesized neurotrophin receptor in the biosynthetic pathway and assists in its membrane targeting. This recycling process is accompanied by transient interaction of galectin-3 with detergent insoluble membrane microdomains in a lactose-and pH-dependent manner. Moreover, in the presence of lactose, apical sorting of the neurotrophin receptor is affected following endosomal deacidification. Taken together, our results suggest that internalized galectin-3 directs the subcellular targeting of apical glycoproteins by membrane recycling.

Galectin-3 Guides Intracellular Trafficking of Some Human Serotransferrin Glycoforms

“…Here galectin-3 binding of transferrin appears to divert the complex directly to Rab11-positive endosomes for faster recycling kinetics. Intriguingly, Rab11 endosomes have previously been recognized as candidate compartments for galectins and glycosylated cargo proteins (44). In support of this we observe a significant overlap between galectin-3-binding transferrin and Rab11 not seen for the non-binding glycoforms.…”

The galectin lattice at a glance

“…In polarized MDCK cells, Gal3 is endocytosed at the apical membrane following activation of a raft-dependent pathway to recycling endosomes (Schneider et al, 2010;Straube et al, 2013). Internalized Gal3 interaction with glycosylated cargo in apical recycling endosomes sorts glycoproteins to the apical membrane (Delacour et al, 2007;Schneider et al, 2010).…”

Galectin-3 in Renal Pathology: More Than Just an Innocent Bystander?

“…An efficiency spectrum of galectin-3 association with binding partners at changing pH values can serve as a tool to regulate lattice formation in cellular compartments [9] . In addition, internalized galectin-3 directs the subcellular targeting of apical glycoproteins by membrane recycling, which is a pH-and lactose-dependent process [17] .…”