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

• Published in: Scientific reports 2016-12, Vol.6 (1), p.39632-39632, Article 39632
• Main Authors: Delage, Elise, Cervantes, Diégo Cordero, Pénard, Esthel, Schmitt, Christine, Syan, Sylvie, Disanza, Andrea, Scita, Giorgio, Zurzolo, Chiara
• Format: Article
• Language: English
• Subjects: 13; 13/109; 13/31; 13/44; 14; 14/19; 14/28; 631/80/128; 631/80/313; Actin; Actin Cytoskeleton - metabolism; Actins - metabolism; Adaptor Proteins, Signal Transducing - metabolism; Animals; Brain - metabolism; Cancer; cdc42 GTP-Binding Protein - metabolism; Cdc42 protein; Cell Adhesion Molecules - metabolism; Cell Communication; Cell Membrane - metabolism; Cell signaling; Endocytosis; Epidermal growth factor; Filopodia; Green Fluorescent Proteins - metabolism; Highways; Humanities and Social Sciences; Kinases; Mice; Microfilament Proteins - metabolism; Microscopy, Electron, Scanning; Molecular modelling; multidisciplinary; Nanotechnology; Nanotubes; Nanotubes - chemistry; Nerve Tissue Proteins - metabolism; Neurodegenerative diseases; Neurons - metabolism; Phosphoproteins - metabolism; Physiology; Proteins; Pseudopodia - metabolism; Science; Signal transduction
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep39632

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.