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Scripps Research scientists have uncovered the workings of a critical process in cell survival. The study show how a protein called talin activates another critical protein, called integrin, to do its job on the cell membrane. While the researchers focused on basic cell biology, the findings suggest targeting a protein like talin to interfere with this activation process, giving scientists a potential way to tackle cancer cells.
The research was led by the laboratory of Tina Izard, PhD, professor on Scripps Research’s Florida campus. The laboratory focuses on understanding the structures and functions of proteins involved in a process called cell adhesion. Without these proteins, cells could not send signals or react to the surrounding environment — cells simply could not function effectively.
A key protein cell adhesion is protein integrin, which is involved in certain cancers and even bleeding disorders. “Integrin activation is a fundamental process in cell biology that also goes awry in important pathological states,” says Izard. “Integrins play key roles in cancer progression and metastasis where certain tumor types exhibit higher levels of certain integrins.”
Talin interacts with the cell membrane to activate integrin, although the detailed molecular mechanisms were unknown. According to Erumbi, it is good to understand talin’s role because talin “glues” integrin to the cytoskeleton within the cells. “By gluing together multiple players, talin brings stability to the cell and helps with functions like cell migration and differentiation.”
The researchers crystallized the domain of talin that interacts with the cell membrane, letting them map out its structure in high resolution using x-ray crystallography. Their structure reveals how talin binds to the cell membrane to activate integrin. Inside the cell, talin exists in a non-activated state defined by interaction between the two ends of talin, its “head domain” and its “tail domain.”
By combining several techniques, the scientists could show that the lipid activates talin by severing this head-tail interaction and exposing a region of talin that binds to integrin. Examining talin could leads to cancer therapies that could target the talin-membrane interaction to stop tumor growth.