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First published online June 3, 2009
doi: 10.1242/10.1242/jcs.044487

Journal of Cell Science 122, 1939-1946 (2009)
Published by The Company of Biologists 2009
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Opinion

Looking beyond death: a morphogenetic role for the TNF signalling pathway

Sam J. Mathew1,*, Dirk Haubert2,{dagger}, Martin Krönke2 and Maria Leptin1,{ddagger}

1 Institute for Genetics, University of Cologne, Zülpicher Strasse 47, D-50674 Köln, Germany
2 Institute for Medical Microbiology, Immunology and Hygiene, Center for Molecular Medicine Cologne, University of Cologne, Goldenfels Strasse 19-21, D-50935 Köln, Germany

{ddagger} Author for correspondence (e-mail: mleptin{at}uni-koeln.de)

Summary

Tumour necrosis factor {alpha} (TNF{alpha}) 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.

Key words: Rho, TRAF4, Cell shape, Cytoskeleton


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© The Company of Biologists Ltd 2009