Fas stimulation of T lymphocytes promotes rapid intercellular exchange of death signals via membrane nanotubes.
The Fas/CD95 surface receptor mediates rapid death of various cell types, including autoreactive T cells with the potential for triggering autoimmunity. Here, we present novel aspects of Fas signalling that define a 'social' dimension to receptor-induced apoptosis. Fas stimulation rapidly induces extensive membrane nanotube formation between neighbouring T cells. This is critically dependent on Rho GTPases but not on caspase activation. Bidirectional transfer of membrane and cytosolic elements including active caspases can be observed to occur via these nanotubes. Nanotube formation and intercellular exchanges of death signals are defective in T lymphocytes from patients with autoimmune lymphoproliferative syndrome harbouring mutations in the Fas receptor. We conclude that nanotube-mediated exchanges constitute a novel form of intercellular communication that augments the propagation of death signalling between neighbouring T cells.
Arkwright
Peter D
PD
University of Manchester, Royal Manchester Children's Hospital, Manchester, United Kingdom.
Luchetti
Francesca
F
Tour
Julien
J
Roberts
Charlotte
C
Ayub
Rahna
R
Morales
Ana P
AP
Rodríguez
José J
JJ
Gilmore
Andrew
A
Canonico
Barbara
B
Papa
Stefano
S
Esposti
Mauro Degli
MD
D017209:Apoptosis / Q000502:physiology*; D056735:Autoimmune Lymphoproliferative Syndrome / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D020169:Caspases / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology*; D002460:Cell Line; D022081:Cell Surface Extensions / Q000276:immunology* / Q000648:ultrastructure*; D002478:Cells, Cultured; D005110:Extracellular Space / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006801:Humans; D019169:Jurkat Cells; D046529:Microscopy, Electron, Transmission; D045333:Nanotubes, Peptide / Q000648:ultrastructure*; D021381:Protein Transport / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology / Q000648:ultrastructure*; D019014:fas Receptor / Q000378:metabolism*; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D045333:Nanotubes, Peptide; D019014:fas Receptor; D020169:Caspases; D020741:rho GTP-Binding Proteins