Tunneling nanotube (TNT) formation is independent of p53 expression

Andresen, Vibeke; Wang, X; Ghimire, Saurav; Omsland, Maria; Gjertsen, Bjørn Tore; Gerdes, Hans‐Hermann

doi:10.1038/cdd.2013.61

Cited by 35 publications

(27 citation statements)

References 7 publications

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“…However, all of these studies were performed in non-neuronal cells (Hela, Jurkat and NK cells). Thus, this apparent discrepancy could simply reflect cell type-dependent mechanisms of TNT formation, as it has been reported for M-Sec and p53-dependent mechanisms2930. It is also worth pointing out that IRSp53, VASP, and Eps8 display context-dependent effects on filopodia formation that may be directly relevant in the context of TNT formation and could account, in part, to an specific cell activity of this actin regulatory signaling axis (see below)3638.…”

Section: Discussionmentioning

confidence: 89%

“…The protein p53 was recently found to play a crucial role in the formation of TNTs in astrocytes via the epidermal growth factor and the Akt/mammalian target of rapamycin (mTor)/phosphatidylinositol 3-kinase (PI3K) pathway19. However, cells that do not express M-Sec, such as the mouse neuronal CAD cell line and neurons, are still capable of forming TNTs29. Furthermore, p53-independent TNT formation was observed in rat pheochromocytoma PC12 cells and in acute myeloid leukemia cells29, suggesting that different molecular mechanisms may be at play.…”

mentioning

confidence: 99%

“…However, cells that do not express M-Sec, such as the mouse neuronal CAD cell line and neurons, are still capable of forming TNTs29. Furthermore, p53-independent TNT formation was observed in rat pheochromocytoma PC12 cells and in acute myeloid leukemia cells29, suggesting that different molecular mechanisms may be at play. Whether different formation mechanisms lead to intercellular connections having distinct functions remains to be determined30.…”

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confidence: 99%

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Differential identity of Filopodia and Tunneling Nanotubes revealed by the opposite functions of actin regulatory complexes

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Cervantes

Pénard

et al. 2016

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Tunneling Nanotubes (TNTs) are actin enriched filopodia-like protrusions that play a pivotal role in long-range intercellular communication. Different pathogens use TNT-like structures as “freeways” to propagate across cells. TNTs are also implicated in cancer and neurodegenerative diseases, making them promising therapeutic targets. Understanding the mechanism of their formation, and their relation with filopodia is of fundamental importance to uncover their physiological function, particularly since filopodia, differently from TNTs, are not able to mediate transfer of cargo between distant cells. Here we studied different regulatory complexes of actin, which play a role in the formation of both these structures. We demonstrate that the filopodia-promoting CDC42/IRSp53/VASP network negatively regulates TNT formation and impairs TNT-mediated intercellular vesicle transfer. Conversely, elevation of Eps8, an actin regulatory protein that inhibits the extension of filopodia in neurons, increases TNT formation. Notably, Eps8-mediated TNT induction requires Eps8 bundling but not its capping activity. Thus, despite their structural similarities, filopodia and TNTs form through distinct molecular mechanisms. Our results further suggest that a switch in the molecular composition in common actin regulatory complexes is critical in driving the formation of either type of membrane protrusion.

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Section: Discussionmentioning

confidence: 89%

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confidence: 99%

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confidence: 99%

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Differential identity of Filopodia and Tunneling Nanotubes revealed by the opposite functions of actin regulatory complexes

Delage

Cervantes

Pénard

et al. 2016

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180

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“…In this regard, Wang et al (2011) revealed that TNT formation between primary rat hippocampal astrocytes and neurons is dependent on the activation of the p53 through H 2 O 2 induced cellular stress . A study by Andresen et al (2013), however showed p53 is dispensable for TNT-formation in SAOS-2 cells and dKO-MSCs (Andresen et al, 2013). Although the p53 and M-Sec proteins have been demonstrated to be important regulators of TNT formation (Gousset et al, 2013;Wang et al, 2011), TNTs have been identified between cells that do not express these proteins, and these suggest that different mechanisms of TNT formation may exist in different cell types (Arkwright et al, 2010).…”

Section: The Molecular Basis Of Tnts Formationmentioning

confidence: 92%

Emerging physiological and pathological implications of tunneling nanotubes formation between cells

Sisakhtnezhad

Khosravi

2015

European Journal of Cell Biology

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“…In some types of neuronal cells such as PC12 cells, TNT formation is independent of p53 expression [108]. However, in astrocytes, it was found that the TNT formation is dependent on p53 activation, a tumour suppressor protein giving cellular and genomic stability [74].…”

Section: (B) Astrocytesmentioning

confidence: 99%

Extracellular-vesicle type of volume transmission and tunnelling-nanotube type of wiring transmission add a new dimension to brain neuro-glial networks

Agnati

Fuxé

2014

Phil. Trans. R. Soc. B

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Two major types of intercellular communication are found in the central nervous system (CNS), namely wiring transmission (WT; point-to-point communication via private channels, e.g. synaptic transmission) and volume transmission (VT; communication in the extracellular fluid and in the cerebrospinal fluid). Volume and synaptic transmission become integrated because their chemical signals activate different types of interacting receptors in heteroreceptor complexes located synaptically and extrasynaptically in the plasma membrane. In VT, we focus on the role of the extracellular-vesicle type of VT, and in WT, on the potential role of the tunnelling-nanotube (TNT) type of WT. The so-called exosomes appear to be the major vesicular carrier for intercellular communication but the larger microvesicles also participate. Extracellular vesicles are released from cultured cortical neurons and different types of glial cells and modulate the signalling of the neuronal -glial networks of the CNS. This type of VT has pathological relevance, and epigenetic mechanisms may participate in the modulation of extracellular-vesicle-mediated VT. Gerdes and co-workers proposed the existence of a novel type of WT based on TNTs, which are straight transcellular channels leading to the formation in vitro of syncytial cellular networks found also in neuronal and glial cultures.

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Tunneling nanotube (TNT) formation is independent of p53 expression

Cited by 35 publications

References 7 publications

Differential identity of Filopodia and Tunneling Nanotubes revealed by the opposite functions of actin regulatory complexes

Differential identity of Filopodia and Tunneling Nanotubes revealed by the opposite functions of actin regulatory complexes

Emerging physiological and pathological implications of tunneling nanotubes formation between cells

Extracellular-vesicle type of volume transmission and tunnelling-nanotube type of wiring transmission add a new dimension to brain neuro-glial networks

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