Galectins in Intra- and Extracellular Vesicles

Abstract

Carbohydrate-binding galectins are expressed in various tissues of multicellular organisms. They are involved in autophagy, cell migration, immune response, inflammation, intracellular transport, and signaling. In recent years, novel roles of galectin-interaction with membrane components have been characterized, which lead to the formation of vesicles with diverse functions. These vesicles are part of intracellular transport pathways, belong to the cellular degradation machinery, or can be released for cell-to-cell communication. Several characteristics of galectins in the lumen or at the membrane of newly formed vesicular structures are discussed in this review and illustrate the need to fully elucidate their contributions at the molecular and structural level.

Keywords: endosome; exosome; galectin; non-classical secretion; sorting.

Figure 1

Galectins sort glycoproteins destined for the apical membrane domain of epithelial cells (A) and recruit the autophagy machinery for autophagosome formation (B). (A) Clustering of lipid raft-associated glycoproteins by galectin-4 or non-raft-glycoproteins by galectin-3 in the lumen of post-Golgi sorting endosomes directs apical cargo molecules into apical transport vesicles. (B) Galectin-mediated glycan detection on damaged endosomes or lysed phagocytic vacuoles recruits the autophagy receptors NDP52, TRIM16, or p62 to initiate nucleation of the phagophore in the cytosol. A phagophore then expands by lipid-acquisition to generate the sealed autophagosome. ER, endoplasmic reticulum; LC3, microtubule-associated protein 1A/1B-light chain 3; N, nucleus; NDP52, nuclear dot protein 52 kDa; P, phagophore; SE; p62, receptor of autophagy; sorting endosome; TGN, trans Golgi network; TRIM16, tripartite motif containing 16.

Figure 2

Exosomal secretion of galectin-3. A conserved P(S/T) AP motif in the amino-terminal region of galectin-3 directly interacts with the endosomal sorting complex required for transport (ESCRT)--component Tsg101. This interaction recruits galectin-3 into newly formed intraluminal vesicles (ILVs) of the multivesicular body (MVB). ILVs are sorted to lysosomes for degradation or released as exosomes into the outer milieu.