TFG is required for autophagy flux and to prevent endoplasmic reticulum stress in CH12 B lymphoma cells.

Steinmetz TD, Schlötzer-Schrehardt U, Hearne A, Schuh W, Wittner J, Schulz SR, Winkler TH, Jäck HM, Mielenz D (2021)
Autophagy 17(9): 2238-2256.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Steinmetz, TD; Schlötzer-Schrehardt, U; Hearne, A; Schuh, W; Wittner, JensUniBi ; Schulz, SR; Winkler, TH; Jäck, HM; Mielenz, D
Abstract / Bemerkung
Plasma cells depend on quality control of newly synthesized antibodies in the endoplasmic reticulum (ER) via macroautophagy/autophagy and proteasomal degradation. The cytosolic adaptor protein TFG (Trk-fused gene) regulates ER-Golgi transport, the secretory pathway and proteasome activity in non-immune cells. We show here that TFG is upregulated during lipopolysaccharide- and CpG-induced differentiation of B1 and B2 B cells into plasmablasts, with the highest expression of TFG in mature plasma cells. CRISPR-CAS9-mediated gene disruption of tfg in the B lymphoma cell line CH12 revealed increased apoptosis, which was reverted by BCL2 but even more by ectopic TFG expression. Loss of TFG disrupted ER structure, leading to an expanded ER and increased expression of ER stress genes. When compared to wild-type CH12 cells, tfg KO CH12 cells were more sensitive toward ER stress induced by tunicamycin, monensin and proteasome inhibition or by expression of an ER-bound immunoglobulin (Ig) μ heavy (µH) chain. CH12 tfg KO B cells displayed more total LC3, lower LC3-II turnover and increased numbers and size of autophagosomes. Tandem-fluorescent-LC3 revealed less accumulation of GFP-LC3 in starved and chloroquine-treated CH12 tfg KO B cells. The GFP:RFP ratio of tandem-fluorescent-LC3 was higher in tunicamycin-treated CH12 tfg KO B cells, suggesting less autophagy flux during induced ER stress. Based on these data, we suggest that TFG controls autophagy flux in CH12 B cells and propose that TFG is a survival factor that alleviates ER stress through the support of autophagy flux in activated B cells and mature plasma cells.
Erscheinungsjahr
2021
Zeitschriftentitel
Autophagy
Band
17
Ausgabe
9
Seite(n)
2238-2256
ISSN
1554-8627
eISSN
1554-8635
Page URI
https://pub.uni-bielefeld.de/record/2969006

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Steinmetz TD, Schlötzer-Schrehardt U, Hearne A, et al. TFG is required for autophagy flux and to prevent endoplasmic reticulum stress in CH12 B lymphoma cells. Autophagy. 2021;17(9):2238-2256.
Steinmetz, T. D., Schlötzer-Schrehardt, U., Hearne, A., Schuh, W., Wittner, J., Schulz, S. R., Winkler, T. H., et al. (2021). TFG is required for autophagy flux and to prevent endoplasmic reticulum stress in CH12 B lymphoma cells. Autophagy, 17(9), 2238-2256. https://doi.org/10.1080/15548627.2020.1821546
Steinmetz, TD, Schlötzer-Schrehardt, U, Hearne, A, Schuh, W, Wittner, Jens, Schulz, SR, Winkler, TH, Jäck, HM, and Mielenz, D. 2021. “TFG is required for autophagy flux and to prevent endoplasmic reticulum stress in CH12 B lymphoma cells.”. Autophagy 17 (9): 2238-2256.
Steinmetz, T. D., Schlötzer-Schrehardt, U., Hearne, A., Schuh, W., Wittner, J., Schulz, S. R., Winkler, T. H., Jäck, H. M., and Mielenz, D. (2021). TFG is required for autophagy flux and to prevent endoplasmic reticulum stress in CH12 B lymphoma cells. Autophagy 17, 2238-2256.
Steinmetz, T.D., et al., 2021. TFG is required for autophagy flux and to prevent endoplasmic reticulum stress in CH12 B lymphoma cells. Autophagy, 17(9), p 2238-2256.
T.D. Steinmetz, et al., “TFG is required for autophagy flux and to prevent endoplasmic reticulum stress in CH12 B lymphoma cells.”, Autophagy, vol. 17, 2021, pp. 2238-2256.
Steinmetz, T.D., Schlötzer-Schrehardt, U., Hearne, A., Schuh, W., Wittner, J., Schulz, S.R., Winkler, T.H., Jäck, H.M., Mielenz, D.: TFG is required for autophagy flux and to prevent endoplasmic reticulum stress in CH12 B lymphoma cells. Autophagy. 17, 2238-2256 (2021).
Steinmetz, TD, Schlötzer-Schrehardt, U, Hearne, A, Schuh, W, Wittner, Jens, Schulz, SR, Winkler, TH, Jäck, HM, and Mielenz, D. “TFG is required for autophagy flux and to prevent endoplasmic reticulum stress in CH12 B lymphoma cells.”. Autophagy 17.9 (2021): 2238-2256.

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