Jiaofeng Chen's research while affiliated with Tsinghua University and other places

... pharmacological agents that target voltage-gated calcium channels is facilitated by a detailed understanding of the molecular structures of these channels, as exemplified by recently published cryo-EM structures of several members of the calcium channel family. [3][4][5] In two recent studies published in Cell Research, Li et al. 6 and Huang et al. 7 expand the current palette of calcium channel structures to two particularly important members -Cav2.1 and Cav3.2 ( Fig. 1). P-and Q-type calcium channels are important for neurotransmitter release in the central and peripheral nervous system, and have been associated with conditions such as familial migraine and ataxia. 1 They are formed by different alternatively spliced variants of the Cav2.1 subunit encoded by the Cacna1a gene, and differ in two important aspects. ...

... 3,[5][6][7][8][9] Precise control of calcium channel activity involves various cellular factors such as receptors, calmodulin, phospholipids, and G proteins. [10][11][12][13][14][15][16][17][18] Additionally, these channels can be modulated by a range of ions, toxins, and numerous clinical and investigational drugs. [19][20][21][22][23][24] Among the 10 mammalian Ca v subtypes (Ca v 1.1-Ca v 1.4, Ca v 2.1-Ca v 2.3, and Ca v 3.1-Ca v 3.3), the Ca v 3 subfamily, also known as the T-type calcium channels, is characterized by tiny and transient currents, in contrast to the large and long-lasting L-type Ca v 1 channels. ...

... Last but not least, small molecule interactions within the scaffold of the spacious cavity have been manifested by the drug-drug interaction between the antiviral sofosbuvir/MNI-1 and the antiarhythmic amiodarone in the PD of Ca v 1 channels. 15,62 Endogenous lipids also represent an important class of small molecules. It is therefore not surprising that one or even more phospholipid molecules might interfere with antagonist binding by modifying the contour and chemical composition of the binding pocket. ...

... In humans, Na V 1.8 is composed of 1956 amino acids, and has a molecular weight of 220 kilodaltons (kDa), though this can vary in other species (Hameed, 2019). The structure of purified human Na V 1.8 has been evaluated using cryogenic electron microscopy and there are unique aspects of the first voltage-sensing domain (VSD1) that appear to modify electrophysiological characteristics of the channel (Huang et al., 2022). Notably, compared with other VGSC isoforms, Na V 1.8 exhibits several distinctive biophysical characteristics, including its activation at a more pronounced state of cellular depolarization, as well as slower inactivation. ...

... Through injecting a gRNA that mainly causes a 1-bp deletion, the frameshift mutation in the hair cells of the mutant mice was corrected. As a result, the auditory and balance functions of the mice were partially rescued [64]. ...

... Such secondary structural transition is also frequently observed in Na v channels bound with pore blockers or even gating modifier toxins which bind to VSDs. 61 The π-form S6 is usually associated with sealed fenestration(s), shrunk cavity volume, and contracted intracellular gate, physical features that all antagonize channel conductance. This observation suggests that the π-form structures might represent potentially more favored templates for Ca v -or Na v -targeting drug design. ...

... • A study on mice by Song et al. showed that L1-induced hearing impairment could actually be reversed by deleting the L1 retrotransposon insertion [13]. • A study by Tao et al. showed that L1 insertions can occur frequently at CRISPR/Cas9 editing sites [14]. ...

... Previous studies of mammalian ultrasonic hearing mainly focused on the cochlea or the evolution of molecular sequences 7,8 ; only a few studies investigated the auditory cortex (ACx) [9][10][11] . As the site of transformation from the auditory scene to its perceptual representation, the ACx is crucial for producing higher cognitive information 12 . ...

... While the function of Tmc1 has been elucidated in a series of studies (22,(26)(27)(28)(29)(30), the function of the Tmc3 protein, particularly in lung-innervation, remains unknown. Based on our knowledge of lung-innervation by Tmc3+ VG we sought to use genetic ablation of Tmc3 followed by NGS sequencing to elucidate the potential roles for TMC3 protein in VGs. ...

... Finally, truncated turtle TMC1/2 proteins, when reconstituted into artificial lipid bilayers, have been reported to form mechanically activated ion channels (Jia et al., 2020). Surprisingly, a study by Liu et al. (2019) suggests that TMC1 provides a leak conductance in hair cells that is sensitive to some of the same cysteine mutations affecting mechanotransduction. A similar function as a leak channel has been reported for TMC proteins in worms (Yue et al., 2018). ...