Galectin-3 (MAC-2) controls phagocytosis and macropinocytosis through intracellular and extracellular mechanisms

Abstract

Galectin-3 (Gal-3; formally named MAC-2) is a β-galactoside-binding lectin. Various cell types produce Gal-3 under either normal conditions and/or pathological conditions. Gal-3 can be present in cells' nuclei and cytoplasm, secreted from producing cells, and associated with cells' plasma membranes. This review focuses on how Gal-3 controls phagocytosis and macropinocytosis. Intracellular and extracellular Gal-3 promotes the phagocytosis of phagocytic targets/cargo (e.g., tissue debris and apoptotic cells) in “professional phagocytes” (e.g., microglia and macrophages) and “non-professional phagocytes” (e.g., Schwann cells and astrocytes). Intracellularly, Gal-3 promotes phagocytosis by controlling the “eat me” signaling pathways that phagocytic receptors generate, directing the cytoskeleton to produce the mechanical forces that drive the structural changes on which phagocytosis depends, protrusion and then retraction of filopodia and lamellipodia as they, respectively, engulf and then internalize phagocytic targets. Extracellularly, Gal-3 promotes phagocytosis by functioning as an opsonin, linking phagocytic targets to phagocytic receptors, activating them to generate the “eat me” signaling pathways. Macropinocytosis is a non-selective endocytic mechanism that various cells use to internalize the bulk of extracellular fluid and included materials/cargo (e.g., dissolved nutrients, proteins, and pathogens). Extracellular and intracellular Gal-3 control macropinocytosis in some types of cancer. Phagocytosed and macropinocytosed targets/cargo that reach lysosomes for degradation may rupture lysosomal membranes. Damaged lysosomal membranes undergo either repair or removal by selective autophagy (i.e., lysophagy) that intracellular Gal-3 controls.

Comprehensive expression analysis with cell-type-specific transcriptome in ALS-linked mutant SOD1 mice: Revisiting the active role of glial cells in disease

“…There are two possible causes of ectopic expression of Mac2 in astrocytes. One is as a result of the normal function of “non-professional phagocytes,” such as astrocytes ( Nguyen et al, 2011 ) and Schwann cells ( Reichert et al, 1994 ), which reactively phagocytose ( Rotshenker, 2022 ). We have shown that in SOD1 G93A mice, astrocytes expressing Mac2 show accumulation of p62, ubiquitin, and mutant SOD1.…”

Fluorescent Chiral Quantum Dots to Unveil Origin-Dependent Exosome Uptake and Cargo Release

“…Gal-3 is a protein that plays crucial roles in cellular functions such as adhesion, proliferation, and inflammation . The binding of Gal-3 on exosomes to αvβ3 integrin on the cell surface resulted in αvβ3 clustering, also known as protein nanoclustering, which leads to Ras signaling followed by macropinocytosis. , Ras and Rac are GTP-binding proteins (GTPases) that play pivotal roles in cell signaling related to the regulation of cell growth, proliferation, cytoskeletal dynamics, and endocytosis . These small GTPases Ras and Rac are crucially involved in macropinocytosis, initiating signaling cascades that lead to this process .…”

Mechanistic Insights into the Role of OPN in Mediating Brain Damage via Triggering Lysosomal Damage in Microglia/Macrophage

“…To explore the function of OPN, the Cytoscape software was used to predict OPN-interacting proteins and the KEGG pathway. The TMT-based quantitative proteomic analysis and PPI network of OPN revealed that a total of 23 DEPs exhibited a potential relationship with OPN, including cathepsins B, L, S, and Z, GAL-3 (GAL-3 is normally a cytosolic protein recruited to damaged lysosomes and triggers selective autophagy [ 22 ]), Galectin-1, and CD44 ( Figure 1 A). Cathepsins B, L, S, and Z are a class of lysosomal cysteine proteases.…”