Cell-to-cell communication is essential for the organization, coordination, and development of cellular networks and multi-cellular systems. Intercellular communication is mediated by soluble factors (including growth factors, neurotransmitters, and cytokines/chemokines), gap junctions, exosomes and recently described tunneling nanotubes (TNTs). It is unknown whether a combination of these communication mechanisms such as TNTs and gap junctions may be important, but further research is required. TNTs are long cytoplasmic bridges that enable long-range, directed communication between connected cells. The proposed functions of TNTs are diverse and not well understood but have been shown to include the cell-to-cell transfer of vesicles, organelles, electrical stimuli and small molecules. However, the exact role of TNTs and gap junctions for intercellular communication and their impact on disease is still uncertain and thus, the subject of much debate. The combined data from numerous laboratories indicate that some TNT mediate a long-range gap junctional communication to coordinate metabolism and signaling, in relation to infectious, genetic, metabolic, cancer, and age-related diseases. This review aims to describe the current knowledge, challenges and future perspectives to characterize and explore this new intercellular communication system and to design TNT-based therapeutic strategies.
Bibliographical noteFunding Information:
Work in Ahmed’s lab is supported by the National Institutes of Child Health and Human (NICHD and National Institute of Health (NIH); Work in MD lab is supported by a national grant from the Netherlands Organization for Scientific Research (“NWO-vici grant”), the KiKa Foundation and the Dutch Cancer Society; Work in SC lab (and SG) is supported by the Cystinosis Research Foundation, the National Institute of Mental Health grants R21-NS090066 and RO1-DK090058, the Sanford Stem Cell Clinical Center and the California Institute of Regenerative Medicine CLIN1-09230; Work in DH lab is funded by The National Institutes of Health grants, CA179087, GM115972, AI132378 and GM119948; Work in EAE lab is supported by The National Institute of Mental Health grant, MH096625, The National Institute of Neurological Disorders and Stroke, NS105584, PHRI funding and a GSK collaboration agreement; Work in KG Lab is supported by the National Institute of General Medical Sciences of the National Institutes of Health under award number SC2GM111144 and a 2014 CSUPERB New Investigator Grant; Work of SK is supported by grants from the Research Foundation for Opto-Science and Technology and the Mochida Memorial Foundation for Medical and Pharmaceutical Research; Work in the EL lab has been supported by grants from The National Center for Advancing Translational Sciences of the National Institutes of Health (Award Number UL1TR000114), Institutional Research Grant #118198-IRG-58-001-52-IRG94 from the American Cancer Society, the National Pancreas Foundation, The Randy Shaver Cancer Research and Community Fund, The Litman Family Fund for Cancer Research, and the University of Minnesota Deborah E. Powell Center for Women’s Health Interdisciplinary Seed Grant support (Grant #PCWH-2013-002); Work in the RM lab is funded by NIH/NIAID, U01-AI35041 04/01/1993— 04/30/2019, Multicenter AIDS Cohort Study (RM is coinvestigator); Work in the GP lab is supported by the Emmy-Noether-Programme of the Deutsche Forschungsgemeinschaft (PR905/1-2); Work in the VAS lab was supported by a grant (No. LIG-13/2012) from the Research Council of Lithuania; Work in the IS lab is funded by National Institutes of Health Grant GM 100201; Work in CZ lab is funded by Agence Nationale de la Recherche (ANR-14-JPCD-0002-01 and ANR-2016-CE160019), Equipe FRM (Fondation Recherche Médicale) 2014 (DEQ20140329557) and a GSK collaboration agreement.
© 2017 Ariazi, Benowitz, De Biasi, Den Boer, Cherqui, Cui, Douillet, Eugenin, Favre, Goodman, Gousset, Hanein, Israel, Kimura, Kirkpatrick, Kuhn, Jeong, Lou, Mailliard, Maio, Okafo, Osswald, Pasquier, Polak, Pradel, de Rooij, Schaeffer, Skeberdis, Smith, Tanveer, Volkmann, Wu and Zurzolo.
- Gap junctions