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Functional cis-heterodimers of N- and R-cadherins
W S Shan1, H Tanaka, G R Phillips
1Department of Biochemistry and Molecular Biology, Program in Cell Adhesion, The Mount Sinai School of Medicine, New York University, New York 10029, USA.
The Journal of Cell Biology
|February 9, 2000
Summary
Researchers discovered that N- and R-cadherins form specific cis-heterodimers, unlike previously known homodimers. This novel cadherin interaction suggests new mechanisms for cell-cell adhesion and function in neural synapses.
Area of Science:
- Molecular Biology
- Cell Biology
- Neuroscience
Background:
- Classical cadherins mediate cell-cell adhesion through cis-dimer formation on cell surfaces.
- Cadherin cis-dimers are considered the active form for adhesion, while monomers are inactive.
- Previously, cis-dimers were only observed between cadherins of the same type.
Purpose of the Study:
- To investigate the potential formation of cis-heterodimers between different cadherin types.
- To explore the functional implications of cadherin cis-heterodimerization in cell adhesion and neural systems.
Main Methods:
- Coexpression of N- and R-cadherins in cells.
- Site-directed mutagenesis to study cis-dimerization mechanisms.
- In vitro coexpression in neurons to observe cadherin localization at synapses.
Main Results:
- Specific cis-heterodimer formation was demonstrated between N-cadherins and R-cadherins.
- E-cadherin was found not to participate in these cis-heterodimeric complexes.
- Coexpressed N- and R-cadherins exhibited homophilic adhesion and coassociation at cell interfaces, with colocalization observed at neural synapses.
Conclusions:
- The study reveals a novel mechanism of cadherin interaction through selective cis-heterodimer formation.
- These cis-heterodimers may represent new functional units mediating specific cell-cell adhesion.
- The findings suggest biological relevance for N- and R-cadherin cis-heterodimers in neural synapse function.