Dynamics of galectin-3 in the nucleus and cytoplasm

Abstract

This review summarizes selected studies on galectin-3 (Gal3) as an example of the dynamic behavior of a carbohydrate-binding protein in the cytoplasm and nucleus of cells. Within the 15-member galectin family of proteins, Gal3 (Mr ~30,000) is the sole representative of the chimera subclass in which a proline- and glycine-rich NH2-terminal domain is fused onto a COOH-terminal carbohydrate recognition domain responsible for binding galactose-containing glycoconjugates. The protein shuttles between the cytoplasm and nucleus on the basis of targeting signals that are recognized by importin(s) for nuclear localization and exportin-1 (CRM1) for nuclear export. Depending on the cell type, specific experimental conditions in vitro, or tissue location, Gal3 has been reported to be exclusively cytoplasmic, predominantly nuclear, or distributed between the two compartments. The nuclear versus cytoplasmic distribution of the protein must reflect, then, some balance between nuclear import and export, as well as mechanisms of cytoplasmic anchorage or binding to a nuclear component. Indeed, a number of ligands have been reported for Gal3 in the cytoplasm and in the nucleus. Most of the ligands appear to bind Gal3, however, through protein-protein interactions rather than through protein-carbohydrate recognition. In the cytoplasm, for example, Gal3 interacts with the apoptosis repressor Bcl-2 and this interaction may be involved in Gal3’s anti-apoptotic activity. In the nucleus, Gal3 is a required pre-mRNA splicing factor; the protein is incorporated into spliceosomes via its association with the U1 small nuclear ribonucleoprotein (snRNP) complex. Although the majority of these interactions occur via the carbohydrate recognition domain of Gal3 and saccharide ligands such as lactose can perturb some of these interactions, the significance of the protein’s carbohydrate-binding activity, per se, remains a challenge for future investigations.

Multiple routes of endocytic internalization of PDGFRβ contribute to PDGF-induced STAT3 signaling

“…As galectin-3 was described to have both extra-and intra-cellular functions (Haudek et al, 2010;Elola et al, 2015) we verified whether addition of soluble recombinant galectin-3 to galectin-3-depleted cells could rescue the observed defect in PDGFRβ endocytosis. As shown in Fig.…”

Galectin-3 maintains cell motility from the subventricular zone to the olfactory bulb

“…Gal-3 is also shuttled back and forth from the cytoplasm to the nucleus where it regulates premRNA splicing (Haudek et al, 2010). Gal-3 becomes strongly…”

Les galectines

“…De façon surprenante, ces deux galectines fonctionneraient comme des facteurs d'épissage des pré-ARNm [5,24,25]. En effet, des extraits nucléaires de cellules HeLa dont on a éliminé les galectines 1 ou 3 présentent un épissage altéré [24,25].…”