Tunneling nanotube (TNT)-mediated neuron-to neuron transfer of pathological Tau protein assemblies.
A given cell makes exchanges with its neighbors through a variety of means ranging from diffusible factors to vesicles. Cells use also tunneling nanotubes (TNTs), filamentous-actin-containing membranous structures that bridge and connect cells. First described in immune cells, TNTs facilitate HIV-1 transfer and are found in various cell types, including neurons. We show that the microtubule-associated protein Tau, a key player in Alzheimer's disease, is a bona fide constituent of TNTs. This is important because Tau appears beside filamentous actin and myosin 10 as a specific marker of these fine protrusions of membranes and cytosol that are difficult to visualize. Furthermore, we observed that exogenous Tau species increase the number of TNTs established between primary neurons, thereby facilitating the intercellular transfer of Tau fibrils. In conclusion, Tau may contribute to the formation and function of the highly dynamic TNTs that may be involved in the prion-like propagation of Tau assemblies.
Université Lille, Inserm, CHU-Lille, UMR-S1172, Alzheimer & Tauopathies, 59000, Lille, France.
Meryem
M
Tardivel
Université Lille, Inserm, CHU-Lille, UMR-S1172, Alzheimer & Tauopathies, 59000, Lille, France.
Séverine
S
Bégard
Paris-Saclay Institute of Neuroscience, Centre National de la Recherche Scientifique, Université Paris-Saclay, 91190, Gif-sur-Yvette, France.
Luc
L
Bousset
Université Lille, Inserm, CHU-Lille, UMR-S1172, Alzheimer & Tauopathies, 59000, Lille, France.|Massachusetts General Hospital, Neurology Department, Mass General Institute for Neurodegenerative Disease, Charlestown, MA, 02129, USA.
Simon
S
Dujardin
Paris-Saclay Institute of Neuroscience, Centre National de la Recherche Scientifique, Université Paris-Saclay, 91190, Gif-sur-Yvette, France.
Audrey
A
Coens
Paris-Saclay Institute of Neuroscience, Centre National de la Recherche Scientifique, Université Paris-Saclay, 91190, Gif-sur-Yvette, France.
Ronald
R
Melki
Université Lille, Inserm, CHU-Lille, UMR-S1172, Alzheimer & Tauopathies, 59000, Lille, France. luc.buee@inserm.fr.|Inserm UMR- S1172, JPArc, 'Alzheimer & Tauopathies', Place de Verdun, 59045, Lille Cedex, France. luc.buee@inserm.fr.
Luc
L
Buée
Université Lille, Inserm, CHU-Lille, UMR-S1172, Alzheimer & Tauopathies, 59000, Lille, France. morvane.colin@inserm.fr.|Inserm UMR- S1172, JPArc, 'Alzheimer & Tauopathies', Place de Verdun, 59045, Lille Cedex, France. morvane.colin@inserm.fr.
Morvane
M
Colin
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002450:Cell Communication; D002460:Cell Line; D002540:Cerebral Cortex / Q000378:metabolism / Q000648:ultrastructure; D005110:Extracellular Space / Q000378:metabolism; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009218:Myosins / Q000378:metabolism; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure*; D017208:Rats, Wistar; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
D000199:Actins; D008164:Luminescent Proteins; C054369:MAPT protein, human; C409064:Myo10 protein, mouse; D014404:Tubulin; C000620630:myosin X, rat; D016875:tau Proteins; D009218:Myosins