Abstract
Cis and trans-interactions in cadherins are the foundations of multicellularity. While the trans-interaction mediate cell-cell adhesion, the cis-interaction is postulated as strengthening to trans by clustering. The well-accepted model in cadherin-adhesion is that the ‘trans precedes cis’ via a diffusion-trap kinetic model. Here we report that cadherin-23, a non-classical cadherin with an extended extracellular region, undergoes clustering in solution via lateral interactions independent of trans and phase separate as liquid droplets. In cellulo using fluorescence-recovery after the photobleaching, we noticed a significantly slow-diffusion of cadherin-23 at the intercellular junctions, indicating the diffusion of a cluster. The cis-clustering accelerates the cell-cell adhesion and, thus, kinetically controls cell-adhesion via ‘cis precedes trans’ model. Though the connection of cis-clustering with the rapid adhesion is yet to explore, M2-macrophages that predominantly express cadherin-23 undergo fast attachments to circulatory tumor cells during metastasis.
Competing Interest Statement
The authors have declared no competing interest.
Abbreviations
- AUC
- Analytical UltraCentrifugation
- Cdh23
- Cadherin-23
- CDF
- Cumulative Distribution Function
- CD
- Cytosolic domain
- DAPI
- 4,6-diamidino-2-phenylindole
- EC
- Extracellular
- EC1-10
- Extracellular 1-10 domains
- EC1-27
- Extracellular 1-27 domains
- eGFP
- Enhanced Green fluorescent protein
- FRAP
- Fluorescence Recovery After Photobleaching
- 1,6-HD
- 1,6-Hexanediol
- ITC
- Isothermal titration calorimetry
- LLPS
- Liquid-Liquid Phase Separation
- Pcdh15
- Protocadherin-15
- qRT-PCR
- Quantitative Real-time polymerase chain reaction
- SPR
- Surface Plamon Resonance
- TM
- Transmembrane