| Autor: |
Helsten, Teresa L., Bunch, Thomas A., Kato, Hisashi, Yamanouchi, Jun, Choi, Sharon H., Jannuzi, Alison L., Féral, Chloe C., Ginsberg, Mark H., Brower, Danny L., Shattil, Sanford J. |
| Zdroj: |
Molecular Biology of the Cell; August 2008, Vol. 19 Issue: 8 p3589-3598, 10p |
| Abstrakt: |
Integrin-mediated cell adhesion is essential for development of multicellular organisms. In worms, flies, and vertebrates, talin forms a physical link between integrin cytoplasmic domains and the actin cytoskeleton. Loss of either integrins or talin leads to similar phenotypes. In vertebrates, talin is also a key regulator of integrin affinity. We used a ligand-mimetic Fab fragment, TWOW-1, to assess talin's role in regulating DrosophilaαPS2βPS affinity. Depletion of cellular metabolic energy reduced TWOW-1 binding, suggesting αPS2βPS affinity is an active process as it is for vertebrate integrins. In contrast to vertebrate integrins, neither talin knockdown by RNA interference nor talin head overexpression had a significant effect on TWOW-1 binding. Furthermore, replacement of the transmembrane or talin-binding cytoplasmic domains of αPS2βPS with those of human αIIbβ3 failed to enable talin regulation of TWOW-1 binding. However, substitution of the extracellular and transmembrane domains of αPS2βPS with those of αIIbβ3 resulted in a constitutively active integrin whose affinity was reduced by talin knockdown. Furthermore, wild-type αIIbβ3 was activated by overexpression of Drosophilatalin head domain. Thus, despite evolutionary conservation of talin's integrin/cytoskeleton linkage function, talin is not sufficient to regulate DrosophilaαPS2βPS affinity because of structural features inherent in the αPS2βPS extracellular and/or transmembrane domains. |
| Databáze: |
Supplemental Index |
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