Abstract
Type 1 tunneling nanotubes (TNTs-1) are long, cytoplasmic protrusions containing actin, microtubules and intermediate filaments that provide a bi-directional road for the transport of various components between distant cells. TNT-1 formation is accompanied by dramatic cytoskeletal reorganization offering mechanical support for intercellular communication. Although the centrosome is the major microtubule nucleating center and also a signaling hub, the relationship between the centrosome and TNTs-1 is still unexplored. We provide here the first evidence of centrosome localization and orientation towards the TNTs-1 protrusion site, which is implicated in TNT-1 formation. We also envision a model whereby synchronized reorientation of the Golgi apparatus along with the centrosome towards TNTs-1 ensures effective polarized trafficking through TNTs-1. Furthermore, using immunohistochemistry and live imaging, we observed for the first time the movement of an extra centrosome within TNTs-1. In this regard, we hypothesize a novel role for TNTs-1 as a critical pathway serving to displace extra centrosomes and potentially to either protect malignant cells against aberrant centrosome amplification or contribute to altering cells in the tumor environment. Indeed, we have observed the increase in binucleation and proliferation markers in receiving cells. The fact that the centrosome can be both as the base and the user of TNTs-1 offers new perspectives and new opportunities to follow in order to improve our knowledge of the pathophysiological mechanisms under TNT control.
Highlights
Our results provide the first evidence of movement of centrosomes within Tunneling nanotubes (TNTs)-1, and lay the foundation for an exciting new research direction for improving our understanding of TNTs formation and their role in carcinogenesis
With regard to the well-established role of centrosome polarization in the asymmetric distribution of stable MTs [11], we hypothesize that a close apposition of the centrosome to the cell cortex probably guided the directionality of microtubules growth toward the site of TNT-1 protrusion
To test this hypothesis and determine whether centrosomes are required for TNT formation, we treated the cells with Centrinone (LCR-263), a selective and reversible inhibitor of polo-like kinase 4 (PLK4), which causes centrosome depletion and arrests cells in a senescence-like G1 state [21]
Summary
The reorientation of the centrosome toward the leading edge of motile cells results in the asymmetric distribution of the MTs as well as the establishment of front–rear cell polarity and oriented trafficking [13,14]. The involvement of the centrosome in the formation of TNTs-1 is still unexplored. Given the increasing evidence indicating a role of TNTs in tumor progression [3,4,10], some fundamental issues, such as the involvement of TNTs-1 in centrosome abnormalities, have to be addressed. Our results provide the first evidence of movement of centrosomes within TNTs-1, and lay the foundation for an exciting new research direction for improving our understanding of TNTs formation and their role in carcinogenesis
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