Subcellular Localization Patterns of Transglutaminase 2 in Astrocytes and Neurons Are Differentially Altered by Hypoxia

Overview

Journal Neuroreport

Specialty Neurology

Date 2017 Sep 29

PMID 28957946

Citations 8

Authors

Laura Yunes-Medina

Julianne Feola

Gail V W Johnson

Affiliations

Soon will be listed here.

Abstract

The multifunctional protein transglutaminase 2 (TG2) has been widely implicated as a modulator of cellular viability. Specifically, TG2 expression is beneficial to neuronal survival following an ischemic injury, whereas the opposite is true in astrocytes. Furthermore, its role in mediating cell death and survival processes has been suggested to be dependent on its subcellular localization. Therefore, the aim of this study was to examine the subcellular localization patterns of neuronal and astrocytic TG2 in ischemia-relevant conditions. We found that nuclear levels of TG2 were significantly increased in neurons, but reduced in astrocytes, in response to hypoxia. In addition, there were no changes in extracellular TG2 in astrocytes exposed to hypoxia. Thus, these findings demonstrate a difference in the subcellular localization pattern of TG2 in neurons and astrocytes in ischemia-relevant conditions and provide further avenues for investigation into the role of TG2 in mediating cellular viability.

Citing Articles

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References

Song Y, Kirkpatrick L, Schilling A, Helseth D, Chabot N, Keillor J . Transglutaminase and polyamination of tubulin: posttranslational modification for stabilizing axonal microtubules. Neuron. 2013; 78(1):109-23. PMC: 3627183. DOI: 10.1016/j.neuron.2013.01.036. View

van Strien M, Drukarch B, Bol J, van der Valk P, van Horssen J, Gerritsen W . Appearance of tissue transglutaminase in astrocytes in multiple sclerosis lesions: a role in cell adhesion and migration?. Brain Pathol. 2010; 21(1):44-54. PMC: 8094321. DOI: 10.1111/j.1750-3639.2010.00428.x. View

Gundemir S, Colak G, Tucholski J, Johnson G . Transglutaminase 2: a molecular Swiss army knife. Biochim Biophys Acta. 2011; 1823(2):406-19. PMC: 3265640. DOI: 10.1016/j.bbamcr.2011.09.012. View

Yakubov B, Chelladurai B, Schmitt J, Emerson R, Turchi J, Matei D . Extracellular tissue transglutaminase activates noncanonical NF-κB signaling and promotes metastasis in ovarian cancer. Neoplasia. 2013; 15(6):609-19. PMC: 3664993. DOI: 10.1593/neo.121878. View

Monteagudo A, Ji C, Akbar A, Keillor J, Johnson G . Inhibition or ablation of transglutaminase 2 impairs astrocyte migration. Biochem Biophys Res Commun. 2016; 482(4):942-947. PMC: 5237609. DOI: 10.1016/j.bbrc.2016.11.137. View

Sochocka E, Juurlink B, Code W, HERTZ V, Peng L, Hertz L . Cell death in primary cultures of mouse neurons and astrocytes during exposure to and 'recovery' from hypoxia, substrate deprivation and simulated ischemia. Brain Res. 1994; 638(1-2):21-8. DOI: 10.1016/0006-8993(94)90628-9. View

Piacentini M, DEletto M, Farrace M, Rodolfo C, Del Nonno F, Ippolito G . Characterization of distinct sub-cellular location of transglutaminase type II: changes in intracellular distribution in physiological and pathological states. Cell Tissue Res. 2014; 358(3):793-805. PMC: 4233112. DOI: 10.1007/s00441-014-1990-x. View

Filiano A, Tucholski J, Dolan P, Colak G, Johnson G . Transglutaminase 2 protects against ischemic stroke. Neurobiol Dis. 2010; 39(3):334-43. PMC: 2917584. DOI: 10.1016/j.nbd.2010.04.018. View

Mautes A, Weinzierl M, Donovan F, Noble L . Vascular events after spinal cord injury: contribution to secondary pathogenesis. Phys Ther. 2000; 80(7):673-87. View

10.

Feola J, Barton A, Akbar A, Keillor J, Johnson G . Transglutaminase 2 modulation of NF-κB signaling in astrocytes is independent of its ability to mediate astrocytic viability in ischemic injury. Brain Res. 2017; 1668:1-11. PMC: 5525061. DOI: 10.1016/j.brainres.2017.05.009. View

11.

Tolentino P, Waghray A, Wang K, Hayes R . Increased expression of tissue-type transglutaminase following middle cerebral artery occlusion in rats. J Neurochem. 2004; 89(5):1301-7. DOI: 10.1111/j.1471-4159.2004.02436.x. View

12.

Hwang I, Yoo K, Yi S, Kim I, Hwang H, Lee K . Expression of tissue-type transglutaminase (tTG) and the effect of tTG inhibitor on the hippocampal CA1 region after transient ischemia in gerbils. Brain Res. 2009; 1263:134-42. DOI: 10.1016/j.brainres.2009.01.038. View

13.

van Strien M, Breve J, Fratantoni S, Schreurs M, Bol J, Jongenelen C . Astrocyte-derived tissue transglutaminase interacts with fibronectin: a role in astrocyte adhesion and migration?. PLoS One. 2011; 6(9):e25037. PMC: 3174992. DOI: 10.1371/journal.pone.0025037. View

14.

Gundemir S, Colak G, Feola J, Blouin R, Johnson G . Transglutaminase 2 facilitates or ameliorates HIF signaling and ischemic cell death depending on its conformation and localization. Biochim Biophys Acta. 2012; 1833(1):1-10. PMC: 3518673. DOI: 10.1016/j.bbamcr.2012.10.011. View

15.

Verderio E, Telci D, Okoye A, Melino G, Griffin M . A novel RGD-independent cel adhesion pathway mediated by fibronectin-bound tissue transglutaminase rescues cells from anoikis. J Biol Chem. 2003; 278(43):42604-14. DOI: 10.1074/jbc.M303303200. View

16.

Eckert R, Kaartinen M, Nurminskaya M, Belkin A, Colak G, Johnson G . Transglutaminase regulation of cell function. Physiol Rev. 2014; 94(2):383-417. PMC: 4044299. DOI: 10.1152/physrev.00019.2013. View

17.

Milakovic T, Tucholski J, McCoy E, Johnson G . Intracellular localization and activity state of tissue transglutaminase differentially impacts cell death. J Biol Chem. 2003; 279(10):8715-22. DOI: 10.1074/jbc.M308479200. View

18.

Gundemir S, Johnson G . Intracellular localization and conformational state of transglutaminase 2: implications for cell death. PLoS One. 2009; 4(7):e6123. PMC: 2701606. DOI: 10.1371/journal.pone.0006123. View

19.

Jones R, Nicholas B, Mian S, Davies P, Griffin M . Reduced expression of tissue transglutaminase in a human endothelial cell line leads to changes in cell spreading, cell adhesion and reduced polymerisation of fibronectin. J Cell Sci. 1997; 110 ( Pt 19):2461-72. DOI: 10.1242/jcs.110.19.2461. View

20.

Belkin A . Extracellular TG2: emerging functions and regulation. FEBS J. 2011; 278(24):4704-16. PMC: 3228878. DOI: 10.1111/j.1742-4658.2011.08346.x. View