Tunnelling nanotubes between neuronal and microglial cells allow bi-directional transfer of α-Synuclein and mitochondria.

Cell Death Dis 2023

Chakraborty R, Nonaka T, Hasegawa M

Abstract

  1. Cell Death Dis. 2023 May 18;14(5):329. doi: 10.1038/s41419-023-05835-8.

Tunnelling nanotubes between neuronal and microglial cells allow bi-directional transfer of α-Synuclein and mitochondria.

Chakraborty R(1)(2), Nonaka T(3), Hasegawa M(3), Zurzolo C(4)(5).

Author information: (1)Institut Pasteur, Université Paris Cité, CNRS UMR 3691, Membrane Traffic and Pathogenesis, Paris, France. (2)Université Paris Saclay, Gif-sur-Yvette, Paris, France. (3)Dementia Research Project, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. (4)Institut Pasteur, Université Paris Cité, CNRS UMR 3691, Membrane Traffic and Pathogenesis, Paris, France. chiara.zurzolo@pasteur.fr. (5)Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy. chiara.zurzolo@pasteur.fr.

Tunnelling Nanotubes (TNTs) facilitate contact-mediated intercellular communication over long distances. Material transfer via TNTs can range from ions and intracellular organelles to protein aggregates and pathogens. Prion-like toxic protein aggregates accumulating in several neurodegenerative pathologies, such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, have been shown to spread via TNTs not only between neurons, but also between neurons-astrocytes, and neurons-pericytes, indicating the importance of TNTs in mediating neuron-glia interactions. TNT-like structures were also reported between microglia, however, their roles in neuron-microglia interaction remain elusive. In this work, we quantitatively characterise microglial TNTs and their cytoskeletal composition, and demonstrate that TNTs form between human neuronal and microglial cells. We show that α-Synuclein (α-Syn) aggregates increase the global TNT-mediated connectivity between cells, along with the number of TNT connections per cell pair. Homotypic TNTs formed between microglial cells, and heterotypic TNTs between neuronal and microglial cells are furthermore shown to

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