Role of Tunneling Nanotubes in the Nervous System
Abstract
:1. Introduction
1.1. TNTs as a Novel Means for Cell Interaction
1.2. TNTs Characteristics
2. Role of TNTs in Nervous System
2.1. Physiological Role: Neurogenesis
2.2. Pathological Role: Aggregates Propagation
2.3. Protective Role: Mitochondrial Transfer
3. Mechanism of TNT Formation in Nervous System
Molecular Pathways and Proteins Important for TNTs
4. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Cell Type | Described Mechanism | Observation | Conclusion | Important Molecule | Ref. |
---|---|---|---|---|---|
PC12 | TNT formation in normal conditions | Block of TNTs formation caused the arrest of organelle transfer | Filopodia are the main precursor of TNTs that further develop into F-actin structures | F-actin | [50] |
PC12 | Rescue from UV stress by TNTs | Stressed cells formed TNTs formation and mitochondria transfer Stressed cells showed very early apoptotic signs, but without caspase-3 activation | TNTs are formed in the cells with damaged mitochondria at early apoptotic stages (before caspase-3 activation) | EB3 | [51] |
PC12, astrocytes | Mitochondria transfer to astrocytes or neuronal cells | Stressed cells formed TNTs formation and to transit mitochondria transfer. Overexpressed Miro1 in MSC improved neurological recovery after stroke | Miro1 is important for the transport of mitochondria in neural cells | Miro1 | [52] |
neurons, astrocytes | Transfer of mitochondria from astrocytes to neurons | Mitochondria transfer from astrocytes to neurons increased neuronal survival in transient focal cerebral ischaemia mice | Astrocytes release extracellular mitochondria via CD38-mediated mechanisms. Integrin-mediated Src/Syk signaling may be involved | CD38 | [53] |
CAD cells | TNT formation in normal conditions | CaMKII regulated TNTs formation. Wnt5a and Wnt7a significantly increased TNTs connections. Wnt7 affected TNTs formation, but not vesicle transfer | Wnt/Ca2+ pathway is involved in actin cytoskeleton remodeling, regulated TNT formation and the transfer of vesicles and α-synuclein aggregates | β isoform of CaMKII, Wnt5a, and Wnt7a | [9] |
neurons | Transfer of mitochondria from MSC to neurons in stress conditions | Stress conditions increased Miro1 and TNFAIP2 expression Miro1 overexpression in MSCs increased mitochondrial transfer | Transfer of mitochondria to oxidant-damaged neurons may help improve neuronal survival and functional recovery after stroke | Miro1 and TNFAIP2 | [54] |
PC12 | TNT formation in normal conditions | TNTs increased in the first 2 h of culture. Myosin Va was present inside TNTs and facilitated organelle transport | TNTs are formed as complex cellular networks. Actin is the major structural component of TNTs | actin and myosin | [4] |
CAD cells | TNT formation in stress conditions | Myo10 overexpression results in the formation of functional TNTs and increased vesicle transfer between cells | TNTs can arise from a subset of Myo10-driven dorsal filopodia, independent of their binding to integrins and N-cadherins | Myo10 | [10] |
CAD cells | TNT formation in normal conditions | Activation of CDC42/IRSp53/VASP network negatively regulates TNTs formation and vesicle transfer. Eps8 increases TNT formation | Although TNTs and filopodia are completely different, the same actin regulators may be involved in their formation | CDC42, IRSp53, VASP, IRSp53, and Eps8 | [55] |
neurons, astrocytes | TNT formation in stress conditions | Stress induced p53 activation, which in turn upregulated EGFR expression and activated downstream pathways stimulating TNT formation | p53 regulates and directly interacts with F-actin during TNT development | p53, Akt, PI3K, and mTOR | [28] |
neurons, astrocytes | TNT formation in both normal and stress conditions | p53 activation induced TNT formation through the activation of caspase-3. Activated caspase-3, by acting on S100A4, created a chemical gradient to direct TNT formation | Extracellular S100A4 directs TNT direction formation and, thus, has a role in TNT guidance | S100A4 | [11] |
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Tarasiuk, O.; Scuteri, A. Role of Tunneling Nanotubes in the Nervous System. Int. J. Mol. Sci. 2022, 23, 12545. https://doi.org/10.3390/ijms232012545
Tarasiuk O, Scuteri A. Role of Tunneling Nanotubes in the Nervous System. International Journal of Molecular Sciences. 2022; 23(20):12545. https://doi.org/10.3390/ijms232012545
Chicago/Turabian StyleTarasiuk, Olga, and Arianna Scuteri. 2022. "Role of Tunneling Nanotubes in the Nervous System" International Journal of Molecular Sciences 23, no. 20: 12545. https://doi.org/10.3390/ijms232012545