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Biol Open. 2014 Nov 13;3(12):1183-95. doi: 10.1242/bio.20149761.

Pre-metazoan origins and evolution of the cadherin adhesome.

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Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA Center of Computational Biology and Bioinformatics, Department of Systems Biology, Columbia University, Irving Cancer Research Center, New York, NY 10032, USA.
Mechanobiology Institute Singapore, National University of Singapore, Singapore 117411 Department of Biomedical Engineering, National University of Singapore, Singapore 117575


Vertebrate adherens junctions mediate cell-cell adhesion via a "classical" cadherin-catenin "core" complex, which is associated with and regulated by a functional network of proteins, collectively named the cadherin adhesome ("cadhesome"). The most basal metazoans have been shown to conserve the cadherin-catenin "core", but little is known about the evolution of the cadhesome. Using a bioinformatics approach based on both sequence and structural analysis, we have traced the evolution of this larger network in 26 organisms, from the uni-cellular ancestors of metazoans, through basal metazoans, to vertebrates. Surprisingly, we show that approximately 70% of the cadhesome, including proteins with similarity to the catenins, predate metazoans. We found that the transition to multicellularity was accompanied by the appearance of a small number of adaptor proteins, and we show how these proteins may have helped to integrate pre-metazoan sub-networks via PDZ domain-peptide interactions. Finally, we found the increase in network complexity in higher metazoans to have been driven primarily by expansion of paralogs. In summary, our analysis helps to explain how the complex protein network associated with cadherin at adherens junctions first came together in the first metazoan and how it evolved into the even more complex mammalian cadhesome.


adherens junction; cadherin; evolution; multicellularity; protein interaction network

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