Nav: Home

Photopharmacology and optogenetics: Lighting the way for second messengers

July 28, 2016

Teams at Ludwig-Maximilians-Universitaet (LMU) in Munich and EMBL have created photosensitive mimics of a class of signaling molecules, thus enabling their actions to be regulated by light, and affording new insights into the communications networks that control cellular metabolism.

Cells react to external stimuli by means of receptors on the plasma membrane, which in turn convey signals - generally referred to as second messengers - into the cytoplasm. Among the most important of these second messengers are the so-called diacylglycerides (DAG), which are enzymatically derived from fat molecules in the cell membrane and are exposed on its inner surface. Changes in the concentration of accessible DAGs result in the activation of signal relays that determine the cell's response to the original extracellular stimulus. Diacylglycerols are directly involved in the regulation of a whole set of essential metabolic processes, including insulin secretion in response to a rise in blood glucose. To facilitate studies of the signaling networks controlled by these messenger molecules, a research team led by Dirk Trauner (Professor of Chemical Biology and Genetics at LMU) and Carsten Schultz (European Molecular Biology Laboratory, Heidelberg) has synthesized derivatives of three diacylglycerols that can be switched between the active and inactive state with the aid of light. This clever approach enables the researchers to control the corresponding signaling pathways in experimental model systems with high precision by means of UV light.

Diacylglycerides form a versatile and widely utilized class of signal molecules in higher organisms. More than 50 structural variants have been identified in human cells. Moreover, because they remain embedded in the membrane, these molecules can interact with its constituents and recruit soluble proteins from the cytoplasm to the membrane. "The spatial conformation of the photo-activatable switches attached to the synthetic diacylglycerides can be reversibly altered by illuminating them with light of different wavelengths," explains James Frank, a member of Trauner's research group and first author on the new paper. The light-sensitive hybrid molecules are inactive in the dark, and are converted into the active form upon exposure to UV light. Irradiation with blue light returns them to the inactive state. "Interestingly, we can also control the subcellular localization of the proteins that bind diacylglycerols, and shunt them from one site in the cell to another - simply with a flash of light," Carsten Schultz adds. The three diacylglycerides that Trauner's group has modified play critical roles in central metabolic processes, such as hormone secretion by the pancreas and signal transmission by nerve cells. With the new compounds, these processes can now be controlled by light in the laboratory. "In the model organism Caenorhabditis elegans, a tiny nematode, we were able to enhance signal transmission via neuromuscular synapses in the living animal using UV light," says Trauner.
-end-


Ludwig-Maximilians-Universität München

Related Proteins Articles:

New method to monitor Alzheimer's proteins
IBS-CINAP research team has reported a new method to identify the aggregation state of amyloid beta (Aβ) proteins in solution.
Composing new proteins with artificial intelligence
Scientists have long studied how to improve proteins or design new ones.
Hero proteins are here to save other proteins
Researchers at the University of Tokyo have discovered a new group of proteins, remarkable for their unusual shape and abilities to protect against protein clumps associated with neurodegenerative diseases in lab experiments.
Designer proteins
David Baker, Professor of Biochemistry at the University of Washington to speak at the AAAS 2020 session, 'Synthetic Biology: Digital Design of Living Systems.' Prof.
Gone fishin' -- for proteins
Casting lines into human cells to snag proteins, a team of Montreal researchers has solved a 20-year-old mystery of cell biology.
Coupled proteins
Researchers from Heidelberg University and Sendai University in Japan used new biotechnological methods to study how human cells react to and further process external signals.
Understanding the power of honey through its proteins
Honey is a culinary staple that can be found in kitchens around the world.
How proteins become embedded in a cell membrane
Many proteins with important biological functions are embedded in a biomembrane in the cells of humans and other living organisms.
Finding the proteins that unpack DNA
A new method allows researchers to systematically identify specialized proteins called 'nuclesome displacing factors' that unpack DNA inside the nucleus of a cell, making the usually dense DNA more accessible for gene expression and other functions.
A brewer's tale of proteins and beer
The transformation of barley grains into beer is an old story, typically starring water, yeast and hops.
More Proteins News and Proteins Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: Reinvention
Change is hard, but it's also an opportunity to discover and reimagine what you thought you knew. From our economy, to music, to even ourselves–this hour TED speakers explore the power of reinvention. Guests include OK Go lead singer Damian Kulash Jr., former college gymnastics coach Valorie Kondos Field, Stockton Mayor Michael Tubbs, and entrepreneur Nick Hanauer.
Now Playing: Science for the People

#562 Superbug to Bedside
By now we're all good and scared about antibiotic resistance, one of the many things coming to get us all. But there's good news, sort of. News antibiotics are coming out! How do they get tested? What does that kind of a trial look like and how does it happen? Host Bethany Brookeshire talks with Matt McCarthy, author of "Superbugs: The Race to Stop an Epidemic", about the ins and outs of testing a new antibiotic in the hospital.
Now Playing: Radiolab

Dispatch 6: Strange Times
Covid has disrupted the most basic routines of our days and nights. But in the middle of a conversation about how to fight the virus, we find a place impervious to the stalled plans and frenetic demands of the outside world. It's a very different kind of front line, where urgent work means moving slow, and time is marked out in tiny pre-planned steps. Then, on a walk through the woods, we consider how the tempo of our lives affects our minds and discover how the beats of biology shape our bodies. This episode was produced with help from Molly Webster and Tracie Hunte. Support Radiolab today at Radiolab.org/donate.