Galectin
They are also termed S-type lectins due to their dependency on disulphide bonds for stability and carbohydrate binding.
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[2] but found primarily in the cytosol, nucleus, extracellular matrix or in circulation.
Tandem galectins contain at least two distinct carbohydrate recognition domains (CRD) within one polypeptide, thus are considered intrinsically divalent.
The concave side forms a groove in which the carbohydrate ligand can bind, and which is long enough to hold about a linear tetrasaccharide.
Crystallisation experiments of galectins in complex with N-acetyllactosamine show that binding arises due to hydrogen bonding interactions from the carbon-4 and carbon-6 hydroxyl groups of galactose and carbon-3 of N-acetylglucosamine (GlcNAc) to the side chains of amino acids in the protein.
Experiments in transgenic mice with deficient N-acetylglucosamine transferase V (GnTV) have increased susceptibility to autoimmune diseases.
Galectin-8 is specific for the glycans bound to integrin and has a direct role in adhesion as well as activating integrin-specific signaling cascades.
Site-directed mutagenesis studies to the carbohydrate recognition domain removes glycan binding but does not prevent association with the spliceosome.
[13] Lysosomal perforation and other endomembrane damage can be inflicted by various agents such as some chemicals yielding osmotically active products, crystalline silica, possibly amyloid aggregates and cytoplasmic organic or inorganic crystals, as well as intracellular microbial pathogens such as Mycobacterium tuberculosis; such injury can be modeled using membrane-permeant dipeptide precursors that polymerize in lysosomes,.
Under resting, homeostatic conditions galectin-8 interacts with mTOR, which in its active state resides on the cytosolic (cytofacial) side of lysosomal membranes.
Evidence suggests that galectin-3 plays a considerable part in processes linked to tumorigenesis, including transformation to a malignant form, metastasis and increased invasive properties of tumour cells.
[16][17] There is some significant evidence that galectin-3 is involved in cancer since it interacts with oncogenes such as Ras and activates downstream signalling that promotes proliferation.
[18] Experiments shows that overexpression of MUC-1 alone is not enough to increase metastatic potential, and in fact it inhibits tumour cell entry into the blood stream.
[18] This is supported by other studies showing that inhibition of galectin-3 in human breast cancer cells lose their malignancy in vitro.
After pathogens, such as bacteria or viruses, are engulfed by cells, they typically try to exit the endosome to gain access to nutrients in the cytosol.
Galectin-8 specifically binds to glycosylation found within the endosome, and recruits adapter molecule CALCOCO2 which activates antibacterial autophagy.
[9] Galectin-3, galectin 8 and galectin-9 have been shown to play additional roles in autophagy both through control of mTOR (galectin-8) and AMPK (galectin-9),[13] and as a factor (galectin-3) in the assembly of the ULK1-Beclin 1-ATG16L1 initiator complex on TRIM16 during endomembrane damage.
HIV is a virus that infects CD4+ cells via binding of its viral envelope glycoprotein complex, which consists of gp120 and gp41.
The gp120 glycoprotein contains two types of N-glycan, high mannose oligomers and N-acetyllactosamine chains on a trimannose core.
[19] The high mannose oligomers are pathogen-associated molecular pattern (PAMPs) and are recognised by the C-type lectin DC-SIGN found on dendritic cells.
[23] Benatar et al. (2015) also demonstrated, however, that T. cruzi-infected murine cardiomyocytes reduce the concentration of surface poly-N-acetyllactosamine, a galectin-1 ligand, within their N- and O-linked glycans, possibly creating a "Gal-1 resistant glycophenotype.
"[23] Also found in abundance in muscle, neurons and kidney[2] Activate apoptosis in T cells[7] Suppression of Th1 and Th17 immune responses[8] Contributes to nuclear splicing of pre-mRNA[24] Found upregulated in tumour cells Regulation of some genes including JNK1[8] Contributes to nuclear splicing of pre-mRNA[24] Crosslinking and adhesive properties In the cytoplasm, helps form the ULK1-Beclin-1-ATG16L1-TRIM16 complex following endomembrane damage[14] Implicated in tuberculosis defense[14] May have a role in apoptosis and cellular repair mediated by p53.
In the cytoplasm, associates upon lysosomal damage with AMPK and activates it[13] Implicated in tuberculosis defense[13][27] Involved in adipocyte differentiation[8]
