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Architecture of cell-cell adhesion in situ
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Cell adhesion is important for the survival of living organisms and plays important roles in cell growth and migration, tissue and organ development, especially in the formation of neural network. In the past decades, hundreds of cell adhesion molecules have been identified, and the structures of many cell adhesion molecules have been solved by crystallography, however, due to technical limitations, how these molecules are organized at cell interfaces and how they regulate the specificity and plasticity of adhesion are not fully understood.  
In a paper published recently in the Proceedings of the National Academy of Sciences USA, scientists from the Shanghai Institute of Biochemistry and Cell Biology, CAS, found that although cell adhesion molecules can be very long with highly flexible conformations, they could mediate compact and stable adhesion interfaces, and different types of domains are playing different roles in forming adhesion interfaces.
The molecules they worked with are called Sidekicks (Sdk1 and Sdk2), which are IgSF molecules and function in the retinal development and motion detection. These molecules have long ectodomains, including six Ig-like domains and thirteen fibronectin domains (FnIII).
By combining multiple biochemical and biophysical techniques such as crystallography, electron microscopy, fluorescence microscopy and electron tomography, researchers were able to generate in situ visualization of the Sdk mediated cell adhesion interfaces. They found that despite Sdk molecules were long and flexible, they were tightly packed in the interfaces. The Ig-like domains behaved like “hooks” to mediate the trans-homophilic pair formation between cells, and the FnIII domains acted as “anchors” associating with membrane and stabilizing the interfaces.
The number and the conformation of the Ig-like domains may reflect the specificity and selectivity of adhesion, while the number of the Fn domains may be relevant to the plasticity or stability of adhesion interfaces. Therefore, the in situ structural model established in this research may represent a generic model for the IgSF adhesion molecules and provide direct structural evidence to understand the mechanisms of adhesion molecules in establishing cell-cell contacts with specificity and plasticity.
This research entitled “Architecture of cell-cell adhesion mediated by sidekicks” was published online on August 27, 2018. It is supported by the grants from the Chinese Academy of Sciences and the National Natural Science Foundation of China.  
Architecture of Sdk-mediated cell adhesion
HE Yongning, Principal Investigator
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences
Shanghai, China
E-mail: he@sibcb.ac.cn


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