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

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...

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Autores principales:	Samer J. Hanna, Kessler McCoy-Simandle, Veronika Miskolci, Peng Guo, Michael Cammer, Louis Hodgson, Dianne Cox
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c22aca1e9c2c436fabe48b56c8490450
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spelling	oai:doaj.org-article:c22aca1e9c2c436fabe48b56c84904502021-12-02T12:32:16ZThe Role of Rho-GTPases and actin polymerization during Macrophage Tunneling Nanotube Biogenesis10.1038/s41598-017-08950-72045-2322https://doaj.org/article/c22aca1e9c2c436fabe48b56c84904502017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08950-7https://doaj.org/toc/2045-2322Abstract 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.Samer J. HannaKessler McCoy-SimandleVeronika MiskolciPeng GuoMichael CammerLouis HodgsonDianne CoxNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-16 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Samer J. Hanna Kessler McCoy-Simandle Veronika Miskolci Peng Guo Michael Cammer Louis Hodgson Dianne Cox The Role of Rho-GTPases and actin polymerization during Macrophage Tunneling Nanotube Biogenesis
description	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.
format	article
author	Samer J. Hanna Kessler McCoy-Simandle Veronika Miskolci Peng Guo Michael Cammer Louis Hodgson Dianne Cox
author_facet	Samer J. Hanna Kessler McCoy-Simandle Veronika Miskolci Peng Guo Michael Cammer Louis Hodgson Dianne Cox
author_sort	Samer J. Hanna
title	The Role of Rho-GTPases and actin polymerization during Macrophage Tunneling Nanotube Biogenesis
title_short	The Role of Rho-GTPases and actin polymerization during Macrophage Tunneling Nanotube Biogenesis
title_full	The Role of Rho-GTPases and actin polymerization during Macrophage Tunneling Nanotube Biogenesis
title_fullStr	The Role of Rho-GTPases and actin polymerization during Macrophage Tunneling Nanotube Biogenesis
title_full_unstemmed	The Role of Rho-GTPases and actin polymerization during Macrophage Tunneling Nanotube Biogenesis
title_sort	role of rho-gtpases and actin polymerization during macrophage tunneling nanotube biogenesis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c22aca1e9c2c436fabe48b56c8490450
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The Role of Rho-GTPases and actin polymerization during Macrophage Tunneling Nanotube Biogenesis

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