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Structural Basis of Latrophilin-FLRT-UNC5 Interaction in Cell Adhesion
Yue C Lu1, Olha V Nazarko1, Richard Sando2
1Department of Biochemistry and Molecular Biology, The University of Chicago, 929 East 57(th) Street, GCIS W219, Chicago, IL 60637, USA.
Structure (London, England : 1993)
|August 4, 2015
Summary
Fibronectin leucine-rich repeat transmembrane proteins (FLRTs) bind to latrophilins (LPHNs) and Uncoordinated-5 (UNC5) receptors. This study reveals FLRT3
Area of Science:
- Neuroscience
- Molecular Biology
- Structural Biology
Background:
- Fibronectin leucine-rich repeat transmembrane proteins (FLRTs) are cell-adhesion molecules crucial for brain development.
- FLRTs mediate neuronal migration and synapse formation through interactions with latrophilins (LPHNs) and Uncoordinated-5 (UNC5) receptors.
Purpose of the Study:
- To elucidate the structural basis of FLRT3 interactions with LPHN3 and UNC5.
- To develop molecular tools for dissecting FLRT/LPHN functions in vivo.
Main Methods:
- X-ray crystallography to determine the structure of FLRT3 alone and in complex with LPHN3.
- Structure-based mutagenesis to analyze protein-protein interactions.
Main Results:
- The crystal structure of the FLRT3/LPHN3 complex shows LPHN3 binding to FLRT3 at a site separate from UNC5.
- Mutations disrupting LPHN3/FLRT3 binding did not affect other interactions or cell localization.
- Evidence suggests FLRT3 can form a trimeric complex with both LPHN3 and UNC5, potentially forming transsynaptic bridges.
Conclusions:
- FLRT3 interacts with LPHN3 and UNC5 through distinct binding sites.
- FLRT3 acts as a scaffold, potentially bridging LPHN3 and UNC5 receptors simultaneously.
- These findings offer molecular insights into the role of FLRTs in synapse development and neuronal migration.
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