Cadherin point mutations alter cell sorting and modulate GTPase signaling

Hamid Tabdili, Adrienne K. Barry, Matthew D. Langer, Yuan Hung Chien, Quanming Shi, Keng Jin Lee, Shaoying Lu, Deborah E. Leckband

Research output: Contribution to journalArticle

Abstract

This study investigated the impact of cadherin binding differences on both cell sorting and GTPase activation. The use of N-terminal domain point mutants of Xenopus C-cadherin enabled us to quantify binding differences and determine their effects on cadherindependent functions without any potential complications arising as a result of differences in cytodomain interactions. Dynamic cell-cell binding measurements carried out with the micropipette manipulation technique quantified the impact of these mutations on the twodimensional binding affinities and dissociation rates of cadherins in the native context of the cell membrane. Pairwise binding affinities were compared with in vitro cell-sorting specificity and ligation-dependent GTPase signaling. Two-dimensional affinity differences greater than five-fold correlated with cadherin-dependent in vitro cell segregation, but smaller differences failed to induce cell sorting. Comparison of the binding affinities with GTPase signaling amplitudes further demonstrated that differential binding also proportionally modulates intracellular signaling. These results show that differential cadherin affinities have broader functional consequences than merely controlling cell-cell cohesion.

Original languageEnglish (US)
Pages (from-to)3299-3309
Number of pages11
JournalJournal of cell science
Volume125
Issue number14
DOIs
StatePublished - Jul 15 2012

Keywords

  • Cadherin
  • Cell sorting
  • GTPase
  • Micropipette manipulation
  • Recognition

ASJC Scopus subject areas

  • Cell Biology

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  • Cite this

    Tabdili, H., Barry, A. K., Langer, M. D., Chien, Y. H., Shi, Q., Lee, K. J., Lu, S., & Leckband, D. E. (2012). Cadherin point mutations alter cell sorting and modulate GTPase signaling. Journal of cell science, 125(14), 3299-3309. https://doi.org/10.1242/jcs.087395