Nucleolin Sculpts Cryptic Intercellular Tunnels

The cells in our bodies communicate in order for the body to stay healthy and functional. A new form of cell-cell communication, named tunneling nanotubes (“TNTs”), was recently discovered. TNTs are thin, hollow tunnels between cells that enable the transport of a variety of “cargoes” between healthy cells of various animals. TNT formation is induced by stress, viral infection and also in cancer. Viruses, malignant cancer cells and neurodegenerative protein clumps (such as those formed in Alzheimer’s, Parkinson’s and Huntington’s diseases) force the infected cells to project many TNTs and subsequently “hijack” them to transmit the disease-causing pathogens to neighboring uninfected cells. It is therefore imperative to understand the molecular pathways that govern TNT formation to understand healthy cells and identify molecular targets to potentially combat disease conditions.

In this study, we discovered that the cellular protein nucleolin is required for TNT formation. We found that nucleolin binds to and stabilizes a key mRNA molecule of the gene 14-3-3 zeta, thus enabling optimum 14-3-3 zeta protein production. 14-3-3 zeta protein further triggers a cascade of molecular “domino” events that ultimately reorganize the cell’s sub-surface actin skeleton to promote TNT outgrowth. Interestingly, we found that key aspects of this mechanism may exist even in certain tissues of roundworms, suggesting that we may have uncovered an important mechanism of TNT formation preserved through evolution. This study could be built upon to understand the development of the animal body, as well as to potentially design new therapeutic interventions.