title: Cadherin point mutations alter cell sorting and modulate GTPase signaling.
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 cadherin-dependent 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 two-dimensional 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.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois, Urbana-Champaign, IL 61801,  USA.
authors.forename: Hamid
authors.initials: H
authors.lastname: Tabdili
authors.forename: Adrienne K
authors.initials: AK
authors.lastname: Barry
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Langer
authors.forename: Yuan-Hung
authors.initials: YH
authors.lastname: Chien
authors.forename: Quanming
authors.initials: Q
authors.lastname: Shi
authors.forename: Keng Jin
authors.initials: KJ
authors.lastname: Lee
authors.forename: Shaoying
authors.initials: S
authors.lastname: Lu
authors.forename: Deborah E
authors.initials: DE
authors.lastname: Leckband
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D002118:Calcium / Q000494:pharmacology; D020013:Calcium Signaling; D002448:Cell Adhesion / Q000502:physiology; D006224:Cricetinae; D004789:Enzyme Activation; D004912:Erythrocytes / Q000166:cytology / Q000378:metabolism / Q000502:physiology; D005434:Flow Cytometry; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006801:Humans; D051379:Mice; D017354:Point Mutation; D015398:Signal Transduction; D014982:Xenopus laevis; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
chemical_list: D015820:Cadherins; D020558:GTP Phosphohydrolases; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein; D002118:Calcium