TMEM16F Regulates Baseline Phosphatidylserine Exposure and Cell Viability in Human Embryonic Kidney Cells.
Background / Aims: TMEM16F is a transmembrane protein from a conserved family of Ca2+-activated proteins, which is highly expressed in several tissues. TMEM16F confers phospholipid scramblase activity and Ca2+-activated electrolyte channel activity. Potentially thereby, TMEM16F is involved in cell cycle control and apoptotic signaling. The present study evaluated the role of TMEM16F on cell proliferation and viability in Human Embryonic Kidney cells.


METHODS
An inducible knockdown of TMEM16F was generated and markers of apoptosis and proliferation were assessed via flow cytometry, western blotting and MTT uptake assay under different conditions.


RESULTS
TMEM16F knockdown resulted in attenuated growth of HEK293 cells. This observation correlated with an increased phosphatidylserine exposure and a decreased fraction of viable cells. Interestingly, the cells were not sensitized to Staurosporine- induced cell death. Western blot analyses displayed a parallel activation of pro- and antiapoptotic signaling pathways: Caspase 3 cleavage and Cyclin D1 abundance were simultaneously increased. Furthermore, knockdown of TMEM16F led to activation of AKT signaling.


CONCLUSIONS
TMEM16F modifies viability of Human Embryonic Kidney cells via its function as a phospholipid scramblase and activation of AKT signaling pathways.
Laura K
LK
Schenk
Ulf
U
Schulze
Sebastian
S
Henke
Thomas
T
Weide
Hermann
H
Pavenstädt
D000075368:Anoctamins; D049109:Cell Proliferation; D002470:Cell Survival; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D010718:Phosphatidylserines / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
C555078:ANO6 protein, human; D000075368:Anoctamins; D010718:Phosphatidylserines; D049294:Phospholipid Transfer Proteins; D051057:Proto-Oncogene Proteins c-akt