TRPC6 Membrane Protein Introduction

Introduction of TRPC6

Short transient receptor potential channel 6 (TRPC6) belongs to the subfamily C of transient receptor potential cation channel (TRP channels). TRPC6 is a nonselective cation channel that allows the influx of Ca²⁺ and Na⁺ ions into the cells via a pore between the fifth and sixth transmembrane domains (TM5-TM6). The cytoplasmic N terminus of TRPC6 has four ankyrin repeats, while the cytoplasmic C terminus has a dystrophin (coiled-coil) domain. It is reported that defects in the TRPC6 gene may contribute to focal segmental glomerulosclerosis 2 (FSGS2).

Function of TRPC6 Membrane Protein

TRPC6 can assemble with other TRPCs or itself to form a nonselective cation channel enabling Ca²⁺ influx into cells. It can be activated by diacylglycerol to transform into an open state. In addition, nephrin is shown to bind to phosphorylated TRPC6 via its cytoplasmic domain, competitively inhibiting TRPC6 expression and activation. TRPC6 is supposed to have a fundamental role in the regulation of smooth muscle tone in blood vessels and lung, and it might act as an important mediator for sensing the extracellular signals that affect synaptic and behavioral plasticity. Different from other members of transient receptor potential cation channel subfamily C, activation of TRPC6 ion channel occurs independently of protein kinase C and it cannot be triggered by depletion of intracellular calcium. TRPC6 is also involved in multiple other biological processes, such as manganese ion transport, regulation of dendrite morphogenesis, neuron differentiation, regulation of cytosolic calcium ion concentration, regulation of peptidyl-threonine phosphorylation, and so on. TRPC6 has been associated with depression and anxiety, as well as with focal segmental glomerulosclerosis (FSGS).

Fig.1 Cryo-EM structure of human TRPC6 at 3.8A resolution. (Tang, 2018)

Application of TRPC6 Membrane Protein in Literature

1. Ji T., et al. TRPC6-Mediated Ca²⁺ Signaling is Required for Hypoxia-Induced Autophagy in Human Podocytes. Cell Physiol Biochem. 2018, 48(4):1782-1792. PubMed ID: 30078002
   
   

   This article finds that down-regulation of TRPC6 by using either a TRPC6 blocker or TRPC6 siRNA can lead to the reduced expression of adenosine monophosphate-activated protein kinase (AMPK), suggesting that the involvement of TRPC6 in hypoxia-induced autophagy in podocytes is associated with AMPK signaling.

2. Ramirez G.A., et al. Ion Channels and Transporters in Inflammation: Special Focus on TRP Channels and TRPC6. Cells. 2018, 7(7). pii: E70. PubMed ID: 29973568
   
   

   This article provides an overview of the interactions between inflammation and ion exchanges with a focus on the pathogenesis of potential future therapeutic implications and immune-mediated diseases.

3. Yin H., et al. Effects of miR-200b-3p inhibition on the TRPC6 and BKCa channels of podocytes. Arch Biochem Biophys. 2018, 653:80-89. PubMed ID: 29958896
   
   

   This article suggests that miR-200 b-3p inhibition can reduce the currents of TRPC6, which then can lead to a decrease of the concentration of intracellular Ca²⁺ and consequently result in the down-regulation of BKCa currents.

4. Verheijden K.A.T., et al. The Calcium-Dependent Protease Calpain-1 Links TRPC6 Activity to Podocyte Injury. J Am Soc Nephrol. 2018, 29(8):2099-2109. PubMed ID: 29954830
   
   

   This article suggests that TRPC6 and/or calpain-1 repression could be options of future therapeutics to treat patients with focal segmental glomerulosclerosis (FSGS) or other podocytopathies.

5. Spires D., et al. The protective role of Trpc6 knockout in the progression of diabetic kidney disease. Am J Physiol Renal Physiol. 2018, 315(4):F1091-F1097. PubMed ID: 29923767
   
   

   This article indicates that repression of TRPC6 channel may have, at least partial, renoprotective effects, which could contribute to the development of new pharmacological tools to prevent or treat the progression of diabetic kidney disease.

TRPC6 Preparation Options

In order to provide high-quality membrane protein preparation service, we have developed a versatile Magic™ membrane protein production platform. Our experienced scientists will do their best to help you find a perfect match in your required formats. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-TRPC6 antibody development services.

• Magic™ Membrane Protein Production Platform
• Magic™ Anti-Membrane Protein Antibody Discovery Platform

Creative Biolabs can provide first-class membrane protein production service using a variety of strategies. Based on our leading-edge platform, we have successfully produced, purified, stabilized and characterized many challenging membrane protein targets for global customers. If you are interested in the service we can provide, please feel free to contact us for more information.

Reference

1. Tang Q, et al. (2018). Structure of the receptor-activated human TRPC6 and TRPC3 ion channels. Cell Res. 28: 746-755.

All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.