2018年4月26日 · Here we present the structure of human TRPC6 homotetramer in complex with a newly identified high-affinity inhibitor BTDM solved by single-particle cryo-electron microscopy to 3.8 Å resolution....

2024年12月25日 · TRPC6 (Transient Receptor Potential Cation Channel Subfamily C Member 6) is a Protein Coding gene. Diseases associated with TRPC6 include Focal Segmental Glomerulosclerosis 2 and Nephrotic Syndrome. Among its related pathways are GPCR downstream signalling and Nervous system development.

TRPC6 is a non-selective cation channel 6 times more permeable to Ca(2+) than to Na(+). Channel homotetramers heterologously expressed have a characteristic doubly rectifying current-voltage relationship and are directly activated by the second messenger diacylglycerol (DAG).

TRPCs are involved in the continually growing number of cell functions. Furthermore, mutations in the TRPC6 gene are associated with hereditary diseases, such as focal segmental glomerulosclerosis. The most important recent breakthrough in TRPC research was the solving of cryo-EM structures of TRPC3, TRPC4, TRPC5, and TRPC6.

TRPC6 is a key mediator of tumor growth of Glioblastoma multiforme; TRPC6 is detected in benign and malignant human prostate tissues and prostate cancer cell lines and is associated with the histological grade, Gleason score and extraprostatic extension of prostate cancer.

Recent advances in cryogenic electron microscopy have provided several high-resolution structures of TRPC channels. Growing evidence demonstrates the involvement of TRPC channels in diseases, particularly the link between genetic mutations of TRPC6 and familial focal segmental glomerulosclerosis.

2022年3月16日 · The gain-of-function (GOF) mutations of TRPC6 lead to familial focal segmental glomerulosclerosis (FSGS) in humans, but their pathogenic mechanism remains elusive. Here, we report the cryo-EM structures of human TRPC3 in both high-calcium and low-calcium conditions.

2007年10月16日 · TRPCs, mammalian homologs of the Drosophila transient receptor potential (trp) protein, are ion channels that are thought to mediate capacitative calcium entry into the cell. Using a PCR-based strategy, Hofmann et al. (1999) isolated cDNAs encoding TRPC6, a novel member of the TRPC family.

Here we report cryo-EM structures of TRPC6 in both antagonist-bound and agonist-bound states. The structures reveal two novel recognition sites for the small-molecule modulators corroborated by mutagenesis data.

TRPC6 is a redox-sensitive channel, and its activation by Reactive Oxygen Species (ROS) overproduction may trigger injury in multiple cells including podocytes . The contributions of TRPC6 channels in glomerular disease progression have been reviewed by Staruschenko et al. .