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Looking beyond death: a morphogenetic role for the TNF signalling pathway.
Sam J Mathew1, Dirk Haubert, Martin Krönke
1Institute for Genetics, University of Cologne, Zülpicher Strasse 47, D-50674 Köln, Germany.
Journal of Cell Science
|June 5, 2009
Summary
Tumour necrosis factor alpha (TNFalpha) signaling controls cell shape, impacting apoptosis and inflammation. This morphogenetic role extends beyond inflammation and is conserved across evolution.
Area of Science:
- Cell Biology
- Molecular Biology
- Evolutionary Biology
Background:
- Tumour necrosis factor alpha (TNFalpha) is a key pro-inflammatory mediator.
- TNFalpha signaling regulates apoptosis and cell shape via cytoskeleton modulation.
- Morphogenetic functions of TNF signaling are increasingly recognized beyond inflammatory contexts.
Purpose of the Study:
- To explore the morphogenetic roles of TNF signaling and related pathways.
- To understand the involvement of Rho-family GTPases in TNF-mediated cell shape changes.
- To investigate the evolutionary origins of TNF signaling functions.
Main Methods:
- Analysis of TNF-receptor superfamily signaling pathways.
- Investigation of adaptor proteins like TNF-receptor-associated factor 4.
- Examination of Rho-family GTPases' role in cell morphology.
Main Results:
- TNF signaling modulates cell shape, a function shared by other TNF-receptor superfamily members.
- Dedicated morphogenetic roles exist for homologous proteins, including ectodysplasin A receptor.
- Rho-family GTPases are central to TNF-induced cell shape alterations.
Conclusions:
- TNF signaling's morphogenetic capacity is evolutionarily conserved, originating from unicellular pathways.
- The ancestral TNF signaling cassette has diversified into overlapping morphogenetic, inflammatory, and apoptotic roles in multicellular organisms.
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