Galectin-8 Explained

Galectin-8 is a protein of the galectin family that in humans is encoded by the LGALS8 gene.^{[1] [2] [3]}

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.^[3]

Galectin-8, interacts with the mTOR regulatory system composed of SLC38A9, Ragulator, RagAB, RagCD.^[4] Galectin-8 controls mTOR causing its inactivation and dissociation from damaged lysosomes, hence transducing the breach of the lysosomal membrane to mTOR. The physiological consequences of mTOR inhibition following lysosomal membrane damage encompass autophagy and metabolic switching.

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.^[5] 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. 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.^[6]

Engineered galectin-8 assays

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.^[7]

Interactions

Galectin-8 has been shown to interact with CD49d,^[8] CD29^[8] and CD49c.^[8] It also interacts with components of the mTORC1 complex.

Further reading

• Bidon N, Brichory F, Bourguet P, Le Pennec JP, Dazord L . Galectin-8: a complex sub-family of galectins (Review) . International Journal of Molecular Medicine . 8 . 3 . 245–50 . September 2001 . 11494049 . 10.3892/ijmm.8.3.245 .
• Danguy A, Camby I, Kiss R . Galectins and cancer . Biochimica et Biophysica Acta (BBA) - General Subjects . 1572 . 2–3 . 285–93 . September 2002 . 12223276 . 10.1016/S0304-4165(02)00315-X .
• Bidon-Wagner N, Le Pennec JP . Human galectin-8 isoforms and cancer . Glycoconjugate Journal . 19 . 7–9 . 557–63 . 2004 . 14758080 . 10.1023/B:GLYC.0000014086.38343.98 . 1330672 .
• Bassen R, Brichory F, Caulet-Maugendre S, Bidon N, Delaval P, Desrues B, Dazord L . Expression of Po66-CBP, a type-8 galectin, in different healthy, tumoral and peritumoral tissues . Anticancer Research . 19 . 6B . 5429–33 . 2000 . 10697573 .
• Hadari YR, Arbel-Goren R, Levy Y, Amsterdam A, Alon R, Zakut R, Zick Y . Galectin-8 binding to integrins inhibits cell adhesion and induces apoptosis . Journal of Cell Science . 113 (Pt 13) . 13 . 2385–97 . July 2000 . 10.1242/jcs.113.13.2385 . 10852818 .
• Gopalkrishnan RV, Roberts T, Tuli S, Kang D, Christiansen KA, Fisher PB . Molecular characterization of prostate carcinoma tumor antigen-1, PCTA-1, a human galectin-8 related gene . Oncogene . 19 . 38 . 4405–16 . September 2000 . 10980616 . 10.1038/sj.onc.1203767 . free .
• Bidon N, Brichory F, Hanash S, Bourguet P, Dazord L, Le Pennec JP . Two messenger RNAs and five isoforms for Po66-CBP, a galectin-8 homolog in a human lung carcinoma cell line . Gene . 274 . 1–2 . 253–62 . August 2001 . 11675018 . 10.1016/S0378-1119(01)00598-4 .
• Nagy N, Bronckart Y, Camby I, Legendre H, Lahm H, Kaltner H, Hadari Y, Van Ham P, Yeaton P, Pector JC, Zick Y, Salmon I, Danguy A, Kiss R, Gabius HJ . 6 . Galectin-8 expression decreases in cancer compared with normal and dysplastic human colon tissue and acts significantly on human colon cancer cell migration as a suppressor . Gut . 50 . 3 . 392–401 . March 2002 . 11839721 . 1773143 . 10.1136/gut.50.3.392 .
• Maier C, Rösch K, Herkommer K, Bochum S, Cancel-Tassin G, Cussenot O, Häussler J, Assum G, Vogel W, Paiss T . 6 . A candidate gene approach within the susceptibility region PCaP on 1q42.2-43 excludes deleterious mutations of the PCTA-1 gene to be responsible for hereditary prostate cancer . European Urology . 42 . 3 . 301–7 . September 2002 . 12234517 . 10.1016/S0302-2838(02)00280-4 .
• Ideo H, Seko A, Ishizuka I, Yamashita K . The N-terminal carbohydrate recognition domain of galectin-8 recognizes specific glycosphingolipids with high affinity . Glycobiology . 13 . 10 . 713–23 . October 2003 . 12851289 . 10.1093/glycob/cwg094 . free .
• Nishi N, Shoji H, Seki M, Itoh A, Miyanaka H, Yuube K, Hirashima M, Nakamura T . 6 . Galectin-8 modulates neutrophil function via interaction with integrin alphaM . Glycobiology . 13 . 11 . 755–63 . November 2003 . 12881409 . 10.1093/glycob/cwg102 . free .

Notes and References

1. Hadari YR, Paz K, Dekel R, Mestrovic T, Accili D, Zick Y . Galectin-8. A new rat lectin, related to galectin-4 . The Journal of Biological Chemistry . 270 . 7 . 3447–53 . February 1995 . 7852431 . 10.1074/jbc.270.7.3447 . free .
2. Su ZZ, Lin J, Shen R, Fisher PE, Goldstein NI, Fisher PB . Surface-epitope masking and expression cloning identifies the human prostate carcinoma tumor antigen gene PCTA-1 a member of the galectin gene family . Proceedings of the National Academy of Sciences of the United States of America . 93 . 14 . 7252–7 . July 1996 . 8692978 . 38969 . 10.1073/pnas.93.14.7252 . 1996PNAS...93.7252S . free .
3. Web site: Entrez Gene: LGALS8 lectin, galactoside-binding, soluble, 8 (galectin 8).
4. Jia J, Abudu YP, Claude-Taupin A, Gu Y, Kumar S, Choi SW, Peters R, Mudd MH, Allers L, Salemi M, Phinney B, Johansen T, Deretic V . 6 . Galectins Control mTOR in Response to Endomembrane Damage . Molecular Cell . 70 . 1 . 120–135.e8 . April 2018 . 29625033 . 5911935 . 10.1016/j.molcel.2018.03.009 .
5. Thurston TL, Wandel MP, von Muhlinen N, Foeglein A, Randow F . Galectin 8 targets damaged vesicles for autophagy to defend cells against bacterial invasion . Nature . 482 . 7385 . 414–8 . January 2012 . 22246324 . 3343631 . 10.1038/nature10744 . 2012Natur.482..414T .
6. Huang J, Brumell JH . Microbiology: A sweet way of sensing danger . Nature . 482 . 7385 . 316–7 . February 2012 . 22337047 . 10.1038/482316a . 2012Natur.482..316H . 33971618 . free .
7. Kilchrist KV, Dimobi SC, Jackson MA, Evans BC, Werfel TA, Dailing EA, Bedingfield SK, Kelly IB, Duvall CL . 6 . Gal8 Visualization of Endosome Disruption Predicts Carrier-Mediated Biologic Drug Intracellular Bioavailability . ACS Nano . 13 . 2 . 1136–1152 . February 2019 . 30629431 . 10.1021/acsnano.8b05482 . 6995262 .
8. Hadari YR, Arbel-Goren R, Levy Y, Amsterdam A, Alon R, Zakut R, Zick Y . Galectin-8 binding to integrins inhibits cell adhesion and induces apoptosis . Journal of Cell Science . 113 (Pt 13) . Pt 13 . 2385–97 . July 2000 . 10.1242/jcs.113.13.2385 . 10852818 .