| LGALS8 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | LGALS8 , Gal-8, PCTA-1, PCTA1, Po66-CBP, galectin 8 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 606099 MGI: 1928481 HomoloGene: 31386 GeneCards: LGALS8 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Galectin-8 is a protein of the galectin family that in humans is encoded by the LGALS8 gene. [5] [6] [7]
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. [7]
Galectin-8, interacts with the mTOR regulatory system composed of SLC38A9, Ragulator, RagAB, RagCD. [8] Galectin-8 controls mTOR causing its inactivation and dissociation from damaged lysosomes, hence transducing the breach of the lysosomal membrane to mTOR. [8] The physiological consequences of mTOR inhibition following lysosomal membrane damage [8] encompass autophagy and metabolic switching.
Galectin-8 has recently been shown to have a role in cellular defence, against both bacterial cytosolic infection and vacuolar damage. [9] 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 vacuoles 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. [9] 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. [9] [10]
Galectin-8 has also been used to study endosomal disruption in the development of nanoscale drug delivery systems. Many drug delivery systems carrying large molecule drugs, such as antisense oligonucleotides, siRNA, peptides, and therapeutic proteins, are engineered to be pH-responsive, and disrupt the endosomal membrane because of the lower pH found within progressively acidifying endosomes. Galectin-8 can be tagged with a fluorophore to track these disrupted endosomal membranes, especially when coupled with automated microscopy. [11]
Galectin-8 has been shown to interact with CD49d, [12] CD29 [12] and CD49c. [12] It also interacts with components of the mTORC1 complex. [8]
Autophagy is the natural, conserved degradation of the cell that removes unnecessary or dysfunctional components through a lysosome-dependent regulated mechanism. It allows the orderly degradation and recycling of cellular components. Although initially characterized as a primordial degradation pathway induced to protect against starvation, it has become increasingly clear that autophagy also plays a major role in the homeostasis of non-starved cells. Defects in autophagy have been linked to various human diseases, including neurodegeneration and cancer, and interest in modulating autophagy as a potential treatment for these diseases has grown rapidly.
The mammalian target of rapamycin (mTOR), also referred to as the mechanistic target of rapamycin, and sometimes called FK506-binding protein 12-rapamycin-associated protein 1 (FRAP1), is a kinase that in humans is encoded by the MTOR gene. mTOR is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases.
Galectins are a class of proteins that bind specifically to β-galactoside sugars, such as N-acetyllactosamine, 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 about 15 galectins discovered in mammals, encoded by the LGALS genes, which are numbered in a consecutive manner. Only galectin-1, -2, -3, -4, -7, -7B, -8, -9, -9B, 9C, -10, -12, -13, -14, and -16 have been identified in humans. Galectin-5 and -6 are found in rodents, whereas galectin-11 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.
Integrin beta-1 (ITGB1), also known as CD29, is a cell surface receptor that in humans is encoded by the ITGB1 gene. This integrin associates with integrin alpha 1 and integrin alpha 2 to form integrin complexes which function as collagen receptors. It also forms dimers with integrin alpha 3 to form integrin receptors for netrin 1 and reelin. These and other integrin beta 1 complexes have been historically known as very late activation (VLA) antigens.
CD49d is an integrin alpha subunit. It makes up half of the α4β1 lymphocyte homing receptor.
Integrin alpha-3 is a protein that in humans is encoded by the ITGA3 gene. ITGA3 is an integrin alpha subunit. Together with beta-1 subunit, it makes up half of the α3β1 integrin duplex that plays a role in neural migration and corticogenesis, acted upon by such factors as netrin-1 and reelin.
Vojo Deretic, is distinguished professor and chair of the Department of Molecular Genetics and Microbiology at the University of New Mexico School of Medicine. Deretic was the founding director of the Autophagy, Inflammation and Metabolism (AIM) Center of Biomedical Research Excellence. The AIM center promotes autophagy research nationally and internationally.
Oxidized low-density lipoprotein receptor 1 also known as lectin-type oxidized LDL receptor 1 (LOX-1) is a protein that in humans is encoded by the OLR1 gene.
Integrin, beta 4 (ITGB4) also known as CD104, is a human gene.
Galectin-3-binding protein is a protein that in humans is encoded by the LGALS3BP gene.
Galectin-9 was first isolated from mouse embryonic kidney in 1997 as a 36 kDa beta-galactoside lectin protein. Human galectin-9 is encoded by the LGALS9 gene.
Regulatory-associated protein of mTOR also known as raptor or KIAA1303 is an adapter protein that is encoded in humans by the RPTOR gene. Two mRNAs from the gene have been identified that encode proteins of 1335 and 1177 amino acids long.
Galectin-2 is a protein that in humans is encoded by the LGALS2 gene.
Integrin alpha-9 is a protein that in humans is encoded by the ITGA9 gene. Cytogenetic location: 3p22.2
Hepatitis A virus cellular receptor 2 (HAVCR2), also known as T-cell immunoglobulin and mucin-domain containing-3 (TIM-3), is a protein that in humans is encoded by the HAVCR2 (TIM-3)gene. HAVCR2 was first described in 2002 as a cell surface molecule expressed on IFNγ producing CD4+ Th1 and CD8+ Tc1 cells. Later, the expression was detected in Th17 cells, regulatory T-cells, and innate immune cells. HAVCR2 receptor is a regulator of the immune response.
Galectin-7 is a protein that in humans is encoded by the LGALS7 gene.
Lysosomal-associated transmembrane protein 4B is a protein that in humans is encoded by the LAPTM4B gene.
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.
mTORC1, also known as mammalian target of rapamycin complex 1 or mechanistic target of rapamycin complex 1, is a protein complex that functions as a nutrient/energy/redox sensor and controls protein synthesis.
Rubicon is a protein that in humans is encoded by the RUBCN gene. Rubicon is one of the few known negative regulators of autophagy, a cellular process that degrades unnecessary or damaged cellular components. Rubicon is recruited to its sites of action through interaction with the small GTPase Rab7, and impairs the autophagosome-lysosome fusion step of autophagy through inhibition of PI3KC3-C2.
