The Role of Rho-GTPases and actin polymerization during Macrophage Tunneling Nanotube Biogenesis

Samer J. Hanna, Kessler McCoy-Simandle, Veronika Miskolci, Peng Guo, Michael Cammer, Louis Hodgson, Dianne Cox

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Macrophage interactions with other cells, either locally or at distances, are imperative in both normal and pathological conditions. While soluble means of communication can transmit signals between different cells, it does not account for all long distance macrophage interactions. Recently described tunneling nanotubes (TNTs) are membranous channels that connect cells together and allow for transfer of signals, vesicles, and organelles. However, very little is known about the mechanism by which these structures are formed. Here we investigated the signaling pathways involved in TNT formation by macrophages using multiple imaging techniques including super-resolution microscopy (3D-SIM) and live-cell imaging including the use of FRET-based Rho GTPase biosensors. We found that formation of TNTs required the activity and differential localization of Cdc42 and Rac1. The downstream Rho GTPase effectors mediating actin polymerization through Arp2/3 nucleation, Wiskott-Aldrich syndrome protein (WASP) and WASP family verprolin-homologous 2 (WAVE2) proteins are also important, and both pathways act together during TNT biogenesis. Finally, TNT function as measured by transfer of cellular material between cells was reduced following depletion of a single factor demonstrating the importance of these factors in TNTs. Given that the characterization of TNT formation is still unclear in the field; this study provides new insights and would enhance the understanding of TNT formation towards investigating new markers.

Original languageEnglish (US)
Article number8547
JournalScientific Reports
Volume7
Issue number1
DOIs
StatePublished - Dec 1 2017

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Nanotubes
rho GTP-Binding Proteins
Polymerization
Actins
Macrophages
Wiskott-Aldrich Syndrome Protein Family
Wiskott-Aldrich Syndrome Protein
Biosensing Techniques
Organelles
Microscopy

ASJC Scopus subject areas

  • General

Cite this

The Role of Rho-GTPases and actin polymerization during Macrophage Tunneling Nanotube Biogenesis. / Hanna, Samer J.; McCoy-Simandle, Kessler; Miskolci, Veronika; Guo, Peng; Cammer, Michael; Hodgson, Louis; Cox, Dianne.

In: Scientific Reports, Vol. 7, No. 1, 8547, 01.12.2017.

Research output: Contribution to journalArticle

Hanna, Samer J. ; McCoy-Simandle, Kessler ; Miskolci, Veronika ; Guo, Peng ; Cammer, Michael ; Hodgson, Louis ; Cox, Dianne. / The Role of Rho-GTPases and actin polymerization during Macrophage Tunneling Nanotube Biogenesis. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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