UC Davis Engineers Make Advances in Cell Adhesion
Proteins that are embedded in cell membranes constitute approximately 20-30% of all human proteins. These membrane proteins, which are essential for cellular survival, mechanically couple cells to each other and also serve as sensors enabling cells to identify signals from the environment. It can be extremely difficult to extract membrane proteins from cell membranes while retaining their biological function, leading them to be poorly studied. In fact, lists of interacting membrane proteins, a key first step in studying their function, are often unknown.
Sanjeevi Sivasankar and Soichiro Yamada, both associate professors in the department of biomedical engineering, decided to take on the challenge of developing a technology capable of discovering membrane protein binding partners on the cell surface. The two-stage process involves generating an initial list of proteins that potentially interact with a membrane protein ‘bait’. The interactions of the bait and their binding partners are then directly measured using an Atomic Force Microscope.
The researchers further tested this new method by using it to identify membrane proteins that bind to the extracellular regions of E-cadherin – an absolutely essential protein that maintains the integrity of tissue. They were able to prove that, contrary to popular belief, the extracellular region of E-cadherin actually binds to a range of membrane proteins; not just identical E-cadherin on opposing cells.
Opportunities to collaborate with colleagues was one of the major motivators in bringing Sivasankar to UC Davis. He and Yamada first met as postdocs at Stanford, so they were both excited to continue working together as faculty at UC Davis. “This project allowed us to integrate some of the sophisticated biophysical expertise in my group with the state-of-the-art molecular and cellular bioengineering tools that [Yamada] has developed in order to address a scientific question that we were both very interested in.”
The results of their research will advance the field of cell adhesion and lead the way for several new avenues of research. The researchers anticipate that this same method can be used to identify binding partners for other essential membrane proteins in a range of cell types. “Now that we have identified novel E-cadherin interactions, it will be interesting to see biophysical characteristics and physiological roles of these proteins,” said Yamada.
In the same spirit of collaboration that first attracted him to UC Davis, Sivasankar made sure to emphasize that “none of this work would have been possible without the efforts of Omer Shafraz, an incredibly talented postdoctoral researcher in my group and the 1st author on the manuscript, who almost single handedly drove this project.”
The full manuscript can be found in the December 8, 2020 issue of PNAS as well as the link below.
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Mapping Transmembrane Binding Partners for E-cadherin Ectodomains