By Matt Wood
Director of Communications, Biological Sciences Division
During animal development, cells divide and arrange themselves in a coordinated way, eventually forming the embryo. The cells communicate with each other during this process through cell-surface receptors, which interact with proteins outside the cell to trigger processes within the developing embryo’s cells at specific times and places. However, the detailed molecular mechanisms behind how cells communicate during early embryonic development are not yet fully understood.
New research from the University of Chicago discovered a novel interaction between two important receptors and investigated their role during embryonic development. One, latrophilin, is an adhesion-type G protein-coupled receptor (aGPCR) that helps cells adhere to each other. The other is a toll-like receptor, which are typically associated with innate immunity.
In a C. elegans nematode worm model, the researchers used biochemical, imaging, and animal studies to see how the two receptors interact in a unique way that hadn’t been observed before. Preventing the receptors from interacting in C. elegans led to significant developmental defects, suggesting that they are crucial for embryo development and nervous system functions.
“We believe we've discovered a cell-to-cell adhesion and communication axis that ensures the body plan properly forms and the animal retains its proper shape and cell to cell contacts,” said one of the senior authors of the study, Engin Özkan, PhD, Associate Professor of Biochemistry and Molecular Biology. The research was published this week in the journal Nature Structural & Molecular Biology.
The new study was led by Gabriel Carmona-Rosas, PhD, a former postdoctoral scholar at UChicago who is now at the University of California, Los Angeles, Jingxian Li, PhD, a staff scientist, and Jayson Smith, PhD, a postdoctoral scholar, both at UChicago. Li works in the lab of Demet Araç, PhD, Associate Professor of Biochemistry and Molecular Biology; Smith works with Paschalis Kratsios, PhD, Associate Professor of Neurobiology. All three labs are associated with UChicago’s Neuroscience Institute.
Using cryo-electron microscopy to capture high-resolution images of the protein structures, they saw that the receptors interacted with each other in a unique way, not how latrophilin and a toll-like receptor would usually connect. This indicated that this interaction could have some other purpose besides the normal innate immune functions.
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