Related Experiment Video
Updated: Sep 17, 2025
Automated Separation of C. elegans Variably Colonized by a Bacterial Pathogen
Published on: March 21, 2014
Structural basis and functional roles for Toll-like receptor binding to Latrophilin in C. elegans development
Gabriel Carmona-Rosas1,2,3, Jingxian Li1,2,3, Jayson J Smith2,4
1Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, USA.
Abstract:
Latrophilins are conserved adhesion-type G-protein-coupled receptors associated with embryonic defects and lethality. However, their mechanistic roles and ligands in embryogenesis remain unknown. Here, we identified TOL-1, the sole Toll-like receptor in Caenorhabditis elegans, as a ligand for the C. elegans latrophilin, LAT-1. The extracellular lectin domain of LAT-1 directly binds to the second leucine-rich repeat domain of TOL-1. The crystal structure and cryo-electron microscopy density map of the LAT-1-TOL-1 extracellular region complex reveal a one-to-one lectin domain interaction with the convex face of a leucine-rich repeat domain. In C. elegans, endogenous mRNA and protein localization analyses showed mutually exclusive sites of expression, suggesting that in vivo LAT-1-TOL-1 interactions mostly occur in trans. Mutagenesis of key interface residues that disrupt the LAT-1-TOL-1 interaction led to partial lethality and malformed embryos. Thus, TOL-1 binding to LAT-1 represents a receptor-ligand axis essential for animal development.
Insights
Toll-like receptor 1 (TOL-1) binds to latrophilin 1 (LAT-1), a G-protein-coupled receptor, revealing a crucial interaction for embryonic development in C. elegans. This receptor-ligand axis is essential for preventing embryonic defects and lethality.
Area of Science:
- Developmental Biology
- Molecular Biology
- Structural Biology
Background:
- Latrophilins are conserved G-protein-coupled receptors involved in embryonic development.
- The specific ligands and mechanistic roles of latrophilins in embryogenesis are largely unknown.
Purpose of the Study:
- To identify the ligand for the Caenorhabditis elegans latrophilin, LAT-1.
- To elucidate the structural basis and functional significance of the LAT-1-ligand interaction in embryonic development.
Main Methods:
- Identified TOL-1 as the sole Toll-like receptor ligand for LAT-1 in C. elegans.
- Determined the crystal structure and cryo-electron microscopy density map of the LAT-1-TOL-1 extracellular complex.
- Performed mutagenesis studies to disrupt the LAT-1-TOL-1 interaction and analyzed embryonic phenotypes.
Main Results:
- The extracellular lectin domain of LAT-1 directly binds to the leucine-rich repeat domain of TOL-1 in a one-to-one interaction.
- LAT-1 and TOL-1 exhibit mutually exclusive expression patterns, suggesting in vivo trans interactions.
- Disruption of the LAT-1-TOL-1 interaction resulted in partial lethality and malformed embryos.
Conclusions:
- TOL-1 is a direct ligand for LAT-1 in C. elegans.
- The LAT-1-TOL-1 receptor-ligand axis is essential for normal embryonic development, preventing lethality and malformations.
Related Concept Videos
01:31Mechanism of Lamellipodia Formation
01:39Mechanism of Filopodia Formation
Their main function is to guide migrating cells during normal tissue morphogenesis or cancer metastasis by recognizing and making initial contacts with the extracellular matrix. However, they can also act as stationary cell anchors or help to establish communication...