期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2011
卷号:108
期号:24
页码:9857-9862
DOI:10.1073/pnas.1019003108
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:Cadherins play a key role in the dynamics of cell-cell contact formation and remodeling of junctions and tissues. Cadherin-cadherin interactions are gated by extracellular Ca2+, which serves to rigidify the cadherin extracellular domains and promote trans junctional interactions. Here we describe the direct visualization and quantification of spatiotemporal dynamics of N-cadherin interactions across intercellular junctions in living cells using a genetically encodable FRET reporter system. Direct measurements of transjunctional cadherin interactions revealed a sudden, but partial, loss of homophilic interactions ({tau} = 1.17 {+/-} 0.06 s-1) upon chelation of extracellular Ca2+. A cadherin mutant with reduced adhesive activity (W2A) exhibited a faster, more substantial loss of homophilic interactions ({tau} = 0.86 {+/-} 0.02 s-1), suggesting two types of native cadherin interactions--one that is rapidly modulated by changes in extracellular Ca2+ and another with relatively stable adhesive activity that is Ca2+ independent. The Ca2+-sensitive dynamics of cadherin interactions were transmitted to the cell interior where {beta}-catenin translocated to N-cadherin at the junction in both cells. These data indicate that cadherins can rapidly convey dynamic information about the extracellular environment to both cells that comprise a junction.
关键词:cell adhesion ; fluorescence resonance energy transfer ; trans binding