A protein that is controlled by both light and temperature can inform cell signaling pathways

The brighter edges of cells in the middle and upper right panels show that photoproteins assemble at the membrane after exposure to light. However, at higher temperatures, the proteins rapidly become inactive and therefore do not remain in the membrane, resulting in faint edges in the lower right panel. Credit: University of Pennsylvania

Most living things contain proteins that react to light. Even organisms that do not have eyes or other visual organs use these proteins to regulate many cellular processes, such as transcription, translation, cell growth, and cell survival.

The field of optogenetics relies on these proteins to better understand and manipulate these processes. Using lasers and genetically modified versions of these naturally occurring proteins, known as probes, researchers can activate and disable a variety of cellular pathways, just like flipping a switch.

Now, Penn Engineering researchers have described a new type of optogenetic protein that can be controlled not only by light, but also by temperature, allowing for a higher degree of control over the processing of cellular pathways. The research will open new horizons for both basic science and translational research.

Lukasz Bugaj, Assistant Professor of Bioengineering (BE), Bomyi Lim, Assistant Professor of Chemical and Biomolecular Engineering, Brian Chow, Associate Professor of BE, graduate students William Benman in the Bugaj Lab, Hao Deng in Lim’s Lab, Erin Berlew and Ivan Kuznetsov in Zhao’s laboratory, they published their study in chemical nature biology. Arndt Siekmann, assistant professor of cell biology and growth at the Perelman School of Medicine, and Caitlyn Parker, a research technician in his lab, also contributed to this research.

The team’s original goal was to develop a single-component probe that would be able to more efficiently process specific cellular pathways. Their probe model was a protein called BcLOV4, and by further investigating the function of this protein, they made a serendipitous discovery: that the protein is controlled by light and temperature.

“Light-activated proteins are a new type of research tool that has increased precision in how we study and understand cell function,” Bogaj says. “Our original goal was to create simpler and more effective tools to control two separate signaling pathways that are essential in cell physiology and usually have a role in cancer.”

Cell signaling pathways, Ras and PI3K, play a role in regulating cell death, so better understanding them may help us understand how healthy cells interact with disease and why cancer cells are constantly growing and spreading.

Conventional probes for these pathways typically include two distinct optical proteins that can require tedious optimization of their relative amounts in the cell. While this improvement is straightforward in individual cells, it is more challenging when looking at tissues or entire organisms.

“Compared with previous probes, our investigations were based on a single protein called BcLOV4, which was recently described by Brian Chao’s lab,” Bogaj says. “As a single protein, BcLOV4 can stimulate signaling in a way that required multiple proteins in previous approaches, making it simpler and easier to use.”

The authors successfully demonstrated that BcLOV4-based probes can induce Ras and PI3K pathways in mammalian cells, as well as in zebrafish and Drosophila, two common model organisms.

“However, in the course of our experiments, we accidentally discovered that BcLOV4 can sense not only light, but also temperature,” says Bujaj. “As far as we know, this kind of dual sensitivity to light and temperature is an entirely new feature of photosensory proteins.”

“The majority of our paper characterizes this dual sensitivity of light and temperature, explores the different experimental systems other than mammalian cells where our tools, such as volatiles and developing zebrafish can be applied, then describes new experimental capabilities that increase light and temperature sensitivity,” he says.

When the team discovered the temperature control in this genetic protein, they modeled different light and temperature conditions to predict how the protein would respond. They also found that by using temperature to deactivate BcLOV4, they could control several photosensitive proteins independently within the same cell.

“For those who study light-sensing proteins, our work provides an example of a protein whose activity responds to two different stimuli, light and temperature, and indicates the possibility of other proteins,” says Bogaj. “This discovery also opens new possibilities for more complex, multi-input remote control of cell function. Our work also has implications for the new field of thermogenetics, or cellular control using temperature, which is already being used as a remote control for engineered cell therapies in animal models” .

“The temperature-sensitive behavior of BcLOV4 is unlike any previously described,” he says. “The protein changes subcellular localization based on temperature, thus heralding an entirely new class of heat-responsive proteins with unique capabilities.”


New proteins enable scientists to control cell activities


more information:
William Benman et al, Temperature-responsive photogenetic probes for cell signaling, chemical nature biology (2021). DOI: 10.1038 / s41589-021-00917-0

Provided by University of Pennsylvania

the quote: a protein controlled by light and temperature can inform cell signaling pathways (2022, January 17) Retrieved on January 18, 2022 from https://phys.org/news/2022-01-protein-temperature-cell-pathways.html

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