Abstract
Tunneling nanotubes (TNTs) can be induced in rat hippocampal astrocytes and neurons with H2O2 or serum depletion. Major cytoskeletal component of TNTs is F-actin. TNTs transfer endoplasmic reticulum, mitochondria, Golgi, endosome and intracellular as well as extracellular amyloid β. TNT development is a property of cells under stress. When two populations of cells are co-cultured, it is the stressed cells that always develop TNTs toward the unstressed cells. p53 is crucial for TNT development. When p53 function is deleted by either dominant negative construct or siRNAs, TNT development is inhibited. In addition, we find that among the genes activated by p53, epidermal growth factor receptor is also important to TNT development. Akt, phosphoinositide 3-kinase and mTOR are involved in TNT induction. Our data suggest that TNTs might be a mechanism for cells to respond to harmful signals and transfer cellular substances or energy to another cell under stress.
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Abbreviations
- Aβ:
-
amyloid β
- ANOVA:
-
analysis of variance
- BCA:
-
bicinchoninic acid
- CBX:
-
carbenoxolone
- EGF:
-
epidermal growth factor
- EGFR:
-
epidermal growth factor receptor
- ER:
-
endoplasmic reticulum
- FBS:
-
fetal bovine serum
- HIV:
-
human immunodeficiency virus
- HRP:
-
horseradish peroxidase
- NGF:
-
nerve growth factor
- PBS:
-
phosphate-buffered saline
- PI3K:
-
phosphoinositide 3-kinase
- TBS:
-
Tris-buffered saline
- TBS-T:
-
Tris-buffered saline with tween20
- TC-Aβ:
-
tetracysteine-amyloid β
- TGF-α:
-
transforming growth factor-α
- TNT:
-
tunneling nanotube
- TUNEL:
-
terminal deoxynucleotidyl transferase-biotin dUTP nick-end labeling
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Acknowledgements
We thank Dr. A Levine (Rockefeller University) for providing wild-type and dominant negative mutant p53 constructs, Dr. J Woodgett (Ontario Cancer Institute) for providing wild-type, dominate negative and constitutively active mutant Akt constructs and Dr. H Lashuel (EPFL) for providing TC-Aβ. We also thank the assistance of confocal imaging from Dr. Shiqiang Wang and Mr. Rongchang Li (Peking University). This work was supported by the National Program of Basic Research sponsored by the Ministry of Science and Technology of China (2009CB941301), Peking University President Research Grant and Ministry of Education Recruiting Research Grant.
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Wang, Y., Cui, J., Sun, X. et al. Tunneling-nanotube development in astrocytes depends on p53 activation. Cell Death Differ 18, 732–742 (2011). https://doi.org/10.1038/cdd.2010.147
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DOI: https://doi.org/10.1038/cdd.2010.147
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