Structural Determination of the Polycystin-2 Channel by Electron Cryo-Microscopy
Jinghua Hu, Yong Yu in Polycystic Kidney Disease, 2019
The TRP channels conduct cations and are grouped into seven subfamilies according to the relatedness of their protein sequences: TRPC (canonical), TRPM (melastatin), TRPA (ankyrin), TRPV (vanilloid), TRPN (NOMPC-like), TRPML (mucolipin), and TRPP (polycystin).44,61 All TRP channel subfamilies, except for TRPN, are present in mammals. In humans, 27 TRP proteins have been identified, making the TRP family the second largest ion channel family, only outnumbered by the potassium-channel family. The TRP channels are sensory proteins that detect and integrate numerous environmental and endogenous stimuli to elicit proper cellular responses. Some TRP channels operate downstream of, or retain the ability to be regulated by, phospholipase C (PLC)-coupled receptors, as first discovered in the ancestral fly TRPs.62,63 However, for most mammalian TRP channels, the in vivo activation mechanisms are yet to be determined.64
Endothelium
Neil Herring, David J. Paterson in Levick's Introduction to Cardiovascular Physiology, 2018
Receptor-operated channels (ROCs) are cation-conducting channels that are activated via a biochemical cascade when an extracellular agent, the ‘agonist’, binds to its specific membrane receptor. Endothelial agonists include histamine, brady- kinin, thrombin, serotonin, adenosine triphosphate (ATP) and ACh. The agonist receptor activates a Gq/11 protein, which activates the membrane-bound enzyme phospholipase C (PLC) (Figure 9.7). PLC splits the phospholipid, phosphatidylinositol bisphosphate, into diacylglycerol (DAG) and inositol 1,4,5 trisphosphate (IP3). DAG activates the ROC ion channel, and IP3 releases Ca2+ from the endoplasmic reticulum. ROCs are poorly selective cation channels that conduct Ca2+ and some Na+ and K+. Since there is a large electrochemical gradient for Ca2+ influx, ROC activation causes a rapid rise in cytosolic [Ca2+]. The ROC constituent proteins were recently identified as members of the transient receptor potential (TRP) C (TRPC) and V (TRPV) families (canonical and vanilloid subtypes).
Ion Channels in Human Pluripotent Stem Cells and Their Neural Derivatives
Tian-Le Xu, Long-Jun Wu in Nonclassical Ion Channels in the Nervous System, 2021
Multipotent NPCs have three possible fates of differentiation: induction into a neuron, astrocyte, or oligodendrocyte. The ion channels, Piezo1, and TRP channels have been detected in hPSC-derived NPCs, and the former has also been shown to greatly influence the fate of differentiation of these NPCs. Piezo1 is a nonclassical ion channel belonging to the stretch-activated channel (SAC) family, which act as nonspecific cationic channels that can be activated by mechanical force (39,40). It was observed that the Piezo1 ion receptor was able to dictate whether neural progenitor cells differentiated into neurons or astrocytes depending on the stiffness of the experienced mechanical force. The fate of these Piezo1-expressing NPCs was determined by the stiffness of their local environment, such as the force exerted by the ECM or adjacent cells (41). The stiffness regulated the elicited inward calcium transient which directed the fate of NPCs. Increasing the stiffness led to an increase in the calcium transient which directed the NPCs toward neurogenesis, while a decrease in stiffness caused a lower calcium influx resulting in an astrocytic fate (41). The canonical transient receptor potential (TRPC) channel was also found to be present in NPCs and its function was implicated in transient calcium influx which controls cell proliferation in NE cells. Transient calcium influx was reduced significantly in hPSC-derived NE cells upon application of TRPC antagonists (42). These findings have implications in developing NPC-based stem cell regenerative medicine, in which NPCs can be transplanted to promote neural repair. Manipulation of Piezo1 channel in NPCs may control their fate after implantation to achieve optimal regenerative effects under disease conditions, while the manipulation of TRPC channels can be used to study their functions in neurodevelopment.
Plasma long non-coding RNAs ASMTL-AS1, AP001363.1, AC005730.3 and AL133415.1 as a potential biomarker for Alzheimer’s disease
Published in Neurological Research, 2023
Yi Cheng, Xiaohui Zhou, Ting Zou, Lei Zhang, Lihua Li, Chang Yang, Long Ma
To reveal the potential roles of these lncRNAs, we performed GO analysis based on the differentially expressed lncRNAs in the plasma. In agreement, our findings also showed that the peripheral blood of AD patients and control groups exhibited differential expression of protein-coding genes. GO enrichment analyses of lncRNAs indicated that homologous recombination, glycine, serine, and threonine metabolism, inflammatory mediator regulation of TRP channels, mismatch repair, and Alzheimer’s disease were significantly affected in the two groups. Transient receptor potential (TRP) channels are divided into 28 members that serve as non-selective calcium channels located on the cell membrane and are highly expressed in brain neurons. Research has shown that TRPC channels are involved in proliferation, intracellular Ca2+ and Mg2+ homeostasis, differentiation, apoptosis, degeneration, and synaptic plasticity in the nervous system [46].
Transient receptor potential canonical 6 knockdown ameliorated diabetic kidney disease by inhibiting nuclear factor of activated T cells 2 expression in glomerular mesangial cells
Published in Renal Failure, 2022
Jian Yu, Chunchun Li, Lisha Ma, Bin Zhai, Aiping Xu, Decui Shao
Transient receptor potential (TRPC) 6, a Ca2+-conductive cation channel, is one member of the seven-member family of TRPCs [7]. Transient receptor potential canonical 6 (TRPC6) is extensively expressed in kidneys, including GMCs, podocytes, and kidney tubular epithelial cells [8]. TRPC6 plays an important role in kidney function control, and TRPC6 dysregulation is associated with kidney pathophysiological changes. TRPC6 mutation results in hereditary focal segmental glomerulosclerosis [9]. The upregulation of TRPC6 is a common feature of patients with proteinuria, and overexpression of TRPC6 in mice causes proteinuria [10]. TRPC6 activation also plays a crucial role in podocyte injury by regulating actin cytoskeleton dynamics [11,12]. Inhibition of TRPC6 in podocytes and kidney tubular epithelial cells can attenuate DKD [13,14]. Previous studies have also shown that TRPC6 regulates the contractile function and proliferation of GMCs [15,16].
The light-activated TRP channel: the founding member of the TRP channel superfamily
Published in Journal of Neurogenetics, 2022
The trp gene was subsequently cloned and molecularly characterized by Montell and Rubin (Montell & Rubin, 1989) and shortly afterward by Wong et al. (1989, for a detailed outline of these studies see (Minke, 2010)). This was an important achievement for it allowed cloning of mammalian genes of the TRP channels superfamily, ultimately leading to the identification of a new subfamily of mammalian trp genes (the TRPC subfamily). However, cloning of the Drosophila trp gene did not lead immediately to the recognition of its function as a light-activated ion channel. Sequencing revealed that the Drosophila trp gene encodes a1275 amino-acid transmembrane protein with no homologies to any known protein in the data base at that time. It had eight transmembrane domains that were later on revised to six trans-membrane segments (S1-6) with a pore region composed of S5-S6 and a pore helix (see Figure 3) and displayed many topological features reminiscent of receptor-transporter-channel proteins. However, the possibility that it might encode a light-activated channel was initially ruled out because light responses were present in trp mutants that showed no protein product in Western blot analyses (Montell & Rubin, 1989). Similarly, Wong et al. (1989) also concluded that ‘functions of the elements in the primary path of excitation … are not dependent on the trp protein’.
Related Knowledge Centers
- Ankyrin
- Diglyceride
- Dihydroxyphenylglycine
- Phospholipase C
- Prefrontal Cortex
- Hippocampus
- Brain
- Transient Receptor Potential Channel
- Ion Channel
- N-Terminus