Abstract
Cis and trans-interactions among cadherins secure multicellularity. While the molecular structure of trans-interactions of cadherins is well understood, identifying the molecular cues that spread the cis-interactions two-dimensionally is still ongoing. Here, we report that transient, weak, multivalent, and spatially distributed hydrophobic interactions, requisite for liquid-liquid phase separations of biomolecules in solution, alone can drive the lateral-clustering of cadherin-23 on a membrane. No specific cis-dimer interactions are required for the lateral clustering. In cellulo, the cis-clustering accelerates the cell-cell adhesion and, thus, contributes in cell-adhesion kinetics along with strengthening the junction. Although the physiological connection of cis-clustering with rapid adhesion is yet to be explored, 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.
Footnotes
The file uploaded was a old version.
Abbreviations
- AUC
- Analytical UltraCentrifugation Cdh23 Cadherin-23
- CDF
- Cumulative Distribution Function CD Cytosolic domain
- EC
- Extracellular
- EC1-27
- Extracellular 1-27 domains
- eGFP
- Enhanced Green fluorescent protein
- FRAP
- Fluorescence Recovery After Photobleaching
- GUV
- Giant unilamellar vesicles
- 1,6-HD
- 1,6-Hexanediol
- ITC
- Isothermal titration calorimetry
- LLPS
- Liquid-liquid Phase Separation
- Pcdh15
- Protocadherin-15
- PICUP
- Photoinduced cross-linking of unmodified proteins
- qRT-PCR
- Quantitative Real-time polymerase chain reaction
- SPR
- Surface Plasmon Resonance
- TM
- Transmembrane