Van Andel Institute Scientists Model ‘Tasty’ Protein that May Lead to New Diabetes Treatments

A team led by scientists at Van Andel Institute (VAI) in Grand Rapids has published the first high-resolution images of TRPM5, a specialized protein concentrated in the tastebuds that relays messages to and from cells, which reveal two areas that may one day lead to improved ways to treat diabetes and other metabolic immune diseases.
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Scientists from the Van Andel Institute in Grand Rapids have published the first high-resolution image of a specialized taste protein called TRPM5, which could lead to new diabetes treatments. // Stock Photo
Scientists from the Van Andel Institute in Grand Rapids have published the first high-resolution image of a specialized taste protein called TRPM5, which could lead to new diabetes treatments. // Stock Photo

A team led by scientists at Van Andel Institute (VAI) in Grand Rapids has published the first high-resolution images of TRPM5, a specialized protein concentrated in the tastebuds that relays messages to and from cells, which reveal two areas that may one day lead to improved ways to treat diabetes and other metabolic immune diseases.

“TRPM5 is the cornerstone of taste signaling, which itself has a much larger role in the body than often recognized,” says Wei Lü, an associate professor at the VAI and co-corresponding author of the study.

“We hope our structures of TRPM5 will serve as blueprints for designing new medications that help control blood sugar in diabetes, while also providing a template for development of low-calorie sweeteners that activate sensory circuits in the brain and the gut — a key distinction that mimics sugar.”

The protein is a key part of the complex process that make up the five types of taste the body senses: sweet, sour, salty, bitter, and umami. Taste perception doesn’t just occur on the tongue, however. Cell called tuft cells coat the linings of the intestine, lungs, and gallbladder, where they employ TRPM5 and related proteins to sense the sugar-like byproducts of parasitic infections which will trigger an immune response.

Juan Du, an associate professor at the VAI and co-corresponding author of the study says that although the body requires sugar, too much is harmful. With a better understanding of the protein, which this model should lead to, a more effective artificial sweetener than what is currently available could be created.

TRPM5 belongs to the TRP superfamily, a group of proteins that mediate responses to sensory stimuli such as pain, pressure, vision, temperature, and taste. TRP proteins and those like them, called ion channels, are located within the cells’ membrane and act as gatekeepers for chemical signals passing in and out.

Lü and Du laboratories have solved the structures of three of the eight known TRPM proteins, and well as an ion channel called CALHM2, which belongs to the calcium homeostasis modulator family. Another member of this molecular family is CALHM1, which is an important component of taste signaling.

Postdoctoral fellow Zheng Ruan, Van Andel Institute Graduate School Ph.D. candidate Emery Haley, and Senior Research Scientist Ian J. Orozco, are co-first authors of the study. Other authors include Mark Sabat, and Richard Myers of Takeda California, Inc., and Rebecca Roth of the VAI. The structures were resolved in collaboration with the David Van Andel Advanced Cryo-Electron Suite at the VAI.

The Van Andel Institute was established in 1996 by the Van Andel family and is now home to more than 400 scientists, educators, and support staff working with national and international collaborators to foster discovery.

Learn more at vai.org.

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