This study is reported by Minmin Luo’s group from the National Institute of Biological Sciences, Beijing (NIBS). Essentially all eukaryotic cells express certain Gq-type G protein-coupled receptors (GPCRs) to mediate responses to hormones, neurotransmitters, sensory stimuli, or cytokines. Many of the Gq-coupled GPCRs are also intensively studied drug targets. Tools for the control of Gq signaling with high temporal and spatial resolution are long-thought goals of life science research. Optogenetics enables temporally precise control of activity in genetically-defined cell populations. Ruicheng Dai, Tao Yu, Danwei Weng, and their colleagues in Luo’s group determined to develop an optogenetic tool for precise control of intracellular Gq signaling.
The team found that expressing cOpn5 in mammalian HEK 293T cells enables blue light-triggered, Gq-dependent calcium release from intracellular stores and protein kinase C activation. Further characterizations revealed that cOpn5 is super-sensitive to blue light (at least 2-3 orders higher sensitivity than those of standard optogenetic tools), responds to light pulses of milliseconds, does not require exogenous chromophore, and enables subcellular control.
“We were absolutely thrilled by the power of chicken opsin 5 to control cellular activity with light so effectively. Most satisfyingly, we made the discovery not by any complicated molecular engineering. It is a pure gift of nature!” Minmin Luo – the lead author of the study – noted.
The authors further demonstrated that cOpn5-mediated optogenetics could be applied to strongly activate neurons and astrocytes, a major type of non-excitable glia cells in the brain. cOpn5 also enabled optical control of mouse feeding behavior in a neural circuit-specific manner. The authors speculated that, given the importance of Gq-coupled receptors in both excitable cells and non-excitable cells, cOpn5 optogenetics may find broad applications in studying the mechanisms and functional relevance of Gq signaling in all tissues and organs.
See the article:
A Neuropsin-based Optogenetic Tool for Precise Control of Gq Signaling
https://link.springer.com/article/10.1007/s11427-022-2122-0
Science China Life Sciences