LGALS8


Description

The LGALS8 (galectin 8) is a protein-coding gene located on chromosome 1.

Galectin-8 is a protein belonging to the galectin family, encoded by the LGALS8 gene in humans. Galectins are beta-galactoside-binding animal lectins with conserved carbohydrate recognition domains. They are involved in various essential functions, including development, differentiation, cell-cell adhesion, cell-matrix interaction, growth regulation, apoptosis, and RNA splicing. LGALS8 is widely expressed in tumoral tissues and seems to play a role in integrin-like cell interactions. Different isoforms are produced through alternative splicing. Galectin-8 interacts with the mTOR regulatory system, which includes SLC38A9, Ragulator, RagAB, and RagCD. It controls mTOR, leading to its inactivation and dissociation from damaged lysosomes, relaying lysosomal membrane damage to mTOR. This inhibition of mTOR following lysosomal membrane damage triggers autophagy and metabolic switching. Recently, Galectin-8 has been identified as a key player in cellular defense against both bacterial cytosolic infection and vacuolar damage. Many intracellular bacteria, such as S. enterica serovar Typhimurium and S. flexneri, replicate inside and outside vacuoles, respectively. However, these vacuoles can become damaged, exposing the bacteria to the host cell cytoplasm. Galectin-8 binds to the damaged vacuole, recruiting autophagy adaptors like NDP52, leading to the formation of an autophagosome and subsequent bacterial destruction.

Galectin-8 acts as a sensor of membrane damage caused by infection, restricting pathogen proliferation by targeting them for autophagy. It detects membrane rupture by binding beta-galactoside ligands exposed on the cytoplasm following endosome membrane rupture. It initiates autophagy via interaction with CALCOCO2/NDP52, restricting infections by bacteria like S.typhimurium and Picornaviridae viruses. It shows a preference for 3'-O-sialylated and 3'-O-sulfated glycans.

LGALS8 is also known as Gal-8, PCTA-1, PCTA1, Po66-CBP.

Associated Diseases



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