We have previously reported that 1-benzyl-2-acetamido-2-deoxy-α-d-galactopyranoside (GalNAcα-O-bn), an inhibitor of glycosylation, perturbed apical biosynthetic trafficking in polarized HT-29 cells suggesting an involvement of a lectin-based mechanism. Here, we have identified galectin-4 as one of the major components of detergent-resistant membranes (DRMs) isolated from HT-29 5M12 cells. Galectin-4 was also found in post-Golgi carrier vesicles. The functional role of galectin-4 in polarized trafficking in HT-29 5M12 cells was studied by using a retrovirus-mediated RNA interference. In galectin-4–depleted HT-29 5M12 cells apical membrane markers accumulated intracellularly. In contrast, basolateral membrane markers were not affected. Moreover, galectin-4 depletion altered the DRM association characteristics of apical proteins. Sulfatides with long chain-hydroxylated fatty acids, which were also enriched in DRMs, were identified as high-affinity ligands for galectin-4. Together, our data propose that interaction between galectin-4 and sulfatides plays a functional role in the clustering of lipid rafts for apical delivery.

Epithelial cells are important building blocks of most tissues and the corner stone of tissue architectures that allow directional transport of nutrients, ions and waste products in and out of the body. In tissues composed of millions of cells every individual cell needs to make right decisions when to differentiate, migrate, divide or die. Tight control of such fundamental cell-level processes ensures proper tissue morphogenesis, homeostasis and function. Cellular decisions are guided by biochemical and mechanical cues from their immediate microenvironment that consists of the extracellular matrix (ECM), neighboring cells and soluble factors. Generation of two distinct surfaces one facing the outside world (the apical domain) and the other contacting the neighboring cells and basal ECM (basolateral domain) is the most fundamental property of epithelial cells. The cues from the ECM are of particular importance in this process and communication between the cells and the ECM is largely mediated by transmembrane ECM receptors. Integrins constitute the largest family of such receptors binding to the ECM. Integrins have been shown to be essential for the establishment of initial polarity cues that define the position of the basal domain and thereby govern the orientation of the forming apico-basal axis. In this review I will discuss the multifaceted roles of integrins in epithelial cells with a particular focus on recent developments unveiling the specific functions of the different integrin heterodimers in regulating epithelial cell polarization and morphogenesis.