Homophilic binding of E-cadherins through their ectodomains is fundamental to epithelial cell–cell adhesion. Despite this, E-cadherin ectodomains have evolved differently in the vertebrate and insect lineages. Of the five rod-like, tandemly aligned extracellular cadherin domains of vertebrate E-cadherin, the tip extracellular cadherin domain plays a pivotal role in binding interactions. Comparatively, the six consecutive N-terminal extracellular cadherin domains of Drosophila E-cadherin, DE-cadherin (also known as Shotgun), can mediate adhesion; however, the underlying mechanism is unknown. Here, we report atomic force microscopy imaging of DE-cadherin extracellular cadherin domains. We identified a tightly folded globular structure formed by the four N-terminal-most extracellular cadherin domains stabilized by the subsequent two extracellular cadherin domains. Analysis of hybrid cadherins from different insects indicated that the E-cadherin globular portion is associated with determining homophilic binding specificity. The second to fourth extracellular cadherin domains were identified as the minimal portion capable of mediating exclusive homophilic binding specificity. Our findings suggest that the N-terminal-most four extracellular cadherin domains of insect E-cadherin are functionally comparable with the N-terminal-most single extracellular cadherin domain of vertebrate E-cadherin, but that their mechanisms might significantly differ. This work illuminates the divergence of structural strategies for E-cadherin homophilic binding among bilaterians.
The authors declare no competing or financial interests.
S.N. and H.O. designed the experiments and performed the molecular and cellular experiments and data analysis. S.N., A.Y. and N.S. conducted the AFM imaging. S.N. and H.O. wrote the manuscript.
This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.
Supplementary information available online at http://jcs.biologists.org/lookup/doi/10.1242/jcs.189258.supplemental
- Received March 11, 2016.
- Accepted July 13, 2016.
- © 2016. Published by The Company of Biologists Ltd