Tunneling nanotubes, an emerging intercellular communication route in development

Abstract

The development of multi-cellular organisms involves a comprehensive and tightly regulated cell-to-cell communication system to coordinate the activity and behavior of individual cells. Diverse signaling pathways ranging from receptor-mediated signal transduction to contact-dependent communication via gap junctions achieve these complex interactions. In this review, we will focus on a new type of intercellular connection, the tunneling nanotube (TNT), which has been observed in many cell types in vitro and recently also in developing embryos of different species in vivo. We will summarize the latest insights into their functional roles in cell-to-cell signaling with a particular focus on the TNT-dependent electrical coupling between developing embryonic cells. Finally, potential implications of these new findings in the light of developmental processes, particularly in cell migration, will be discussed.

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

“…Some of these structures formed distinct intercellular bridges between MHC class IIþ dendritic cells. Furthermore, a number of in vivo studies demonstrate TNT-like structures during developmental processes in embryogenic tissues of vertebrates and invertebrates [107].…”

“…Developing hippocampal neurons were demonstrated to form transient nanotubes with distant astrocytes [107,111]. TNTs were found to mediate both transient calcium signals and depolarization from distant astrocytes to neurons within a limited maturation period.…”

Tunneling nanotube (TNT) formation is independent of p53 expression

“…In support of this, several cell lines are reported to form TNTs express mutated or inactive p53. 2,3 Thus, substantial evidence suggests that p53 is not a master protein for TNT formation and further investigation is needed to dissect the molecular mechanisms underlying their formation.…”

“…The recent discovery that TNT-like structures exist in vivo suggests they may have an important role during tissue development and maintenance. 2,3 TNTs facilitate intercellular transfer of various cellular components and are thought to represent a novel form of cellular communication. [1][2][3] Recently, it was reported that TNT formation in primary rat hippocampal astrocytes and neurons was dependent on the activation of tumor suppressor protein p53 through cellular stress induction such as hydrogen peroxide (H 2 O 2 ).…”

“…2,3 TNTs facilitate intercellular transfer of various cellular components and are thought to represent a novel form of cellular communication. [1][2][3] Recently, it was reported that TNT formation in primary rat hippocampal astrocytes and neurons was dependent on the activation of tumor suppressor protein p53 through cellular stress induction such as hydrogen peroxide (H 2 O 2 ). 4 Considering the broad effect of p53 on numerous cellular functions, 5 we here investigated whether p53 is a key protein needed for TNT formation.…”