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The canonical transient receptor potential channel TRPC is a non-selective cation channel permeable to calcium ions1, with the highest sequence similarity to the TRP channel first discovered in the Drosophila photoreceptor system, and can be used by second messengers.
On January 19, 2022, the research group of Chen Lei from the Joint Center for Life Sciences and the Institute of Molecular Medicine, School of Future Technology, Peking University, reported the structural mechanism of Ca2+ regulation of human TRPC3/6 and the pathogenic mechanism of FSGS-related mutants in the journal Neuron.
In the process of studying TRPC3/6 channels, the authors used the inside-out patch-clamp technique to find that Ca2+ on the cytoplasmic side can inhibit the background current of TRPC3 channel, while the background current of TRPC6 channel shows low-concentration activation and high-concentration inhibition phenomenon
Finally, the authors solved the high-resolution structure (2.
In summary, through structural analysis and functional verification, this study determined that TRPC3/6 channels have an inhibitory Ca2+ binding site CBS1 in the cytoplasmic region
Figure 1.
The first author of this study is Guo Wenjun, a doctoral student at the Institute of Molecular Medicine, School of Future Technology, Peking University; doctoral students Tang Qinglin, Wei Miao, postdoctoral fellows Kang Yunlu and Wu Jingxiang participated in some experiments; and researcher Chen Lei is the corresponding author
Chen Lei's laboratory mainly studies the working mechanism of membrane proteins, especially important membrane proteins related to metabolic diseases and cardiovascular diseases (http://
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