New Tool Illuminates Cell Signaling Pathways Key to Disease

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In a major advance for fundamental biological research, UC San Francisco scientists have developed a tool capable of illuminating previously inscrutable cellular signaling networks that play a wide variety of roles in human biology and disease. In particular, the technique opens up exciting new avenues for understanding and treating psychiatric disease, the researchers say.

The new technology, described in a paper published April 6, 2016 in Cell, makes it vastly easier for scientists to study the complex workings of a large family of sensor proteins called G-protein-coupled receptors (GPCRs), which sit in cell membranes and enable cells to respond to chemical signals from other parts of the body or the outside world. In a first proof-of-principle study, the UCSF team used their new approach to identify new biochemical players involved in the development of tolerance to opioid painkillers — which target a particular type of GPCR — findings they anticipate will enable researchers to develop safer and more effective pain control.

“This technology will let us understand how these critical signaling molecules work in a way we’ve never been able to before,” said Nevan Krogan, PhD, a professor of cellular and molecular pharmacology and director of the Quantitative Biosciences Institute (QBI) at UCSF and a senior investigator at the Gladstone Institutes, who was one of the new paper’s senior authors.

Roughly 800 different types of GPCR play crucial roles throughout the body, including regulating heart rate, blood pressure and digestion; mediating the senses of sight, smell, and taste; and enabling many forms of chemical communication between cells in the brain. Approximately 40 percent of medicines target one type of GPCR or another, including schizophrenia drugs that target dopamine receptors, painkillers that target opioid receptors, and allergy and heartburn drugs that target different types of histamine receptors, just to name a few.

These many types of GPCR have one feature in common that makes them ...

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