Looking beyond death: a morphogenetic role for the TNF signalling pathway.
Tumour necrosis factor alpha (TNFalpha) is a pro-inflammatory mediator with the capacity to induce apoptosis. An integral part of its apoptotic and inflammatory programmes is the control of cell shape through modulation of the cytoskeleton, but it is now becoming apparent that this morphogenetic function of TNF signalling is also employed outside inflammatory responses and is shared by the signalling pathways of other members of the TNF-receptor superfamily. Some proteins that are homologous to the components of the TNF signalling pathway, such as the adaptor TNF-receptor-associated factor 4 and the ectodysplasin A receptor (and its ligand and adaptors), have dedicated morphogenetic roles. The mechanism by which TNF signalling affects cell shape is not yet fully understood, but Rho-family GTPases have a central role. The fact that the components of the TNF signalling pathway are evolutionarily old suggests that an ancestral cassette from unicellular organisms has diversified its functions into partly overlapping morphogenetic, inflammatory and apoptotic roles in multicellular higher organisms.
Mathew
Sam J
SJ
Institute for Genetics, University of Cologne, Zülpicher Strasse 47, D-50674 Köln, Germany.
Haubert
Dirk
D
Krönke
Martin
M
Leptin
Maria
M
D008841:Actin Cytoskeleton / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D048430:Cell Shape / Q000235:genetics / Q000502:physiology*; D003599:Cytoskeleton / Q000502:physiology; D006801:Humans; D008954:Models, Biological; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D018124:Receptors, Tumor Necrosis Factor; D047988:Tumor Necrosis Factor Receptor-Associated Peptides and Proteins; D014409:Tumor Necrosis Factor-alpha