Glycobiological axis in adipose tissue: structural, biochemical and functional characterization of Galectin-12

BANNOUD, NADIA; PIETRASANTA, LÍA I.; SUNDBLAD, VICTORIA; MALLER, SEBASTIÁN M.; PÉREZ SÁEZ, JUAN M.; DI LELLA, SANTIAGO; MARIÑO, KARINA V.; CAGNONI, ALEJANDRO J.; SIGAUT, LORENA; CROCI, DIEGO O.; RABINOVICH, GABRIEL A.

San Luis

Congreso; XLVIII Reunión Anual de la Sociedad Argentina de Biofísica; 2019

Sociedad Argentina de Biofísica

Lectins, endogenous glycan-binding proteins, can decipher and convey glycan-containing information into biologically relevant cellular programs. Galectins are a family of soluble lectins de ned by a common structural fold and a conserved carbohydrate recognition domain (CRD), capable of recognizing N- and O-glycans bearing the disaccharide Nacetyllactosamine. By interacting with cell surface glycoconjugates, these lectins control a myriad of cellular processes including endocytosis and cell signaling cascades, leading to regulation of cellular activation, proliferation, migration, and survival. Based on theirmolecular architecture, galectins have been classi ed into three di!erent structural groups: (i) proto-type galectins, which contain a single CRD and are capable of dimerizing; (ii) chimera-type galectins, with a single CRD, which are able to form pentamers; and (iii) tandem-repeat type galectins, with two CRDs of di!erent nature in the same polypeptidic chain. Glycan speci city of each member of the family is dictated by differences in the architecture and dynamics of the ligand-binding groove (LBG). While some galectin members are ubiquitously expressed, other galectins show preferential expression in certain tissues or cell types. Among these, galectin-12 (Gal-12) is preferentially localized in adipose tissue and plays a key role in adipocyte differentiation, lipolysis and glucose homeostasis. Compared to other galectins, Gal-12 has been historically out of the spotlight due to the lack of publically available crystal structure and the di"culties for its recombinant expression. In spite of these drawbacks, we have studied the biochemical and biophysical determinants of their structure, glycan speci city and subcellular localization and identi ed its pro-angiogenic function within adipose tissue. Surprisingly, and distinct from other members of the galectin family, Gal-12 revealed preferential recognition of 3-fucosylated N-acetyllactosamine (LacNAc) structures, that are highly represented in endothelial cells. Using complementary experimental and theoretical approaches, our studies unveil atomistic, biochemical and topological features of a hypoxia-regulated lectin in adipose tissue that controls endothelial cell function via recognition of 3-fucosylated glycans.