Galectin

Galectins are a family of proteins defined by their binding specificity for β-galactoside sugars, such as N-acetyllactosamine (Galβ1-3GlcNAc or Galβ1-4GlcNAc), which can be bound to proteins by either N-linked or O-linked glycosylation. They are also termed S-type lectins due to their dependency on disulphide bonds for stability and carbohydrate binding. There have been 15 galectins discovered in mammals, encoded by the LGALS genes, which are numbered in a consecutive manner. Only galectin-1, -2, -3, -4, -7, -8, -9, -10, -12 and -13 have been identified in humans. Galectin-5 and -6 are found in rodents, whereas galectin-11, -14 and -15 are uniquely found in sheep and goats. Members of the galectin family have also been discovered in other mammals, birds, amphibians, fish, nematodes, sponges, and some fungi. Unlike the majority of lectins they are not membrane bound, but soluble proteins with both intra- and extracellular functions. They have distinct but overlapping distributions but found primarily in the cytosol, nucleus, extracellular matrix or in circulation. Although many galectins must be secreted, they do not have a typical signal peptide required for classical secretion. The mechanism and reason for this non-classical secretion pathway is unknown.

Galectin-3

Galectin-3 is a protein that in humans is encoded by the LGALS3 gene. Galectin-3 is a member of the lectin family, of which 14 mammalian galectins have been identified.

Galectin-3 is approximately 30 kDa and, like all galectins, contains a carbohydrate-recognition-binding domain (CRD) of about 130 amino acids that enable the specific binding of β-galactosides.

Galectin-3 (Gal-3) is also a member of the beta-galactoside-binding protein family that plays an important role in cell-cell adhesion, cell-matrix interactions, macrophage activation, angiogenesis, metastasis, apoptosis.

Galectin-3 is encoded by a single gene, LGALS3, located on chromosome 14, locus q21–q22. Galectin-3 is expressed in the nucleus, cytoplasm, mitochondrion, cell surface, and extracellular space.

Function

Galectin-3 has an affinity for beta-galactosides and exhibits antimicrobial activity against bacteria and fungi.

This protein has been shown to be involved in the following biological processes: cell adhesion, cell activation and chemoattraction, cell growth and differentiation, cell cycle, and apoptosis. Given galectin-3’s broad biological functionality, it has been demonstrated to be involved in cancer, inflammation and fibrosis, heart disease, and stroke. Studies have also shown that the expression of galectin-3 is implicated in a variety of processes associated with heart failure, including myofibroblast proliferation, fibrogenesis, tissue repair, inflammation, and ventricular remodeling.

Galectin-8

Galectin-8 is a protein of the galectin family that in humans is encoded by the LGALS8 gene.

Function

This gene encodes a member of the galectin family. Galectins are beta-galactoside-binding animal lectins with conserved carbohydrate recognition domains. The galectins have been implicated in many essential functions including development, differentiation, cell-cell adhesion, cell-matrix interaction, growth regulation, apoptosis, and RNA splicing. This gene is widely expressed in tumoral tissues and seems to be involved in integrin-like cell interactions. Alternatively spliced transcript variants encoding different isoforms have been identified.

Role in cellular defence

Galectin-8 has recently been shown to have a role in cellular defence, against both bacterial cytosolic infection and vacuolar damage. Many intracellular bacteria, such as S. enterica serovar Typhimurium and S. flexneri prefer to replicate inside and outside of the vacuole safety respectively, yet these vacoles may become damaged, exposing bacteria to the host cell cytoplasm. It has been shown that the binding of galectin-8 to the damaged vacuole can recruit autophagy adaptors such as NDP52 leading to the formation of an autophagosome and subsequent bacterial destruction. As knockout experiments of galectin-8 leads to more successful cytosolic replication by S. enterica serovar Typhimurium, it is thought that galectin-8 acts as a danger receptor in defence against intracellular pathogens.