TRPV6 Membrane Protein Introduction

Introduction of TRPV6

TRPV6 (transient receptor potential vanilloid 6) has six transmembrane helices and a pore-forming loop between transmembrane segments 5 and 6 and intracellularly located amino and carboxy terminal ends. Four TRPV6 proteins co-assemble to a tetrameric channel with a single ion conducting pore. Most TRP channels are Ca²⁺ permeable, but only two, TRPV5 (synonyms ECaC1, CaT2) and TRPV6 (synonyms ECaC2, CaT1, CaT-like), are highly Ca²⁺-selective with Ca²⁺/Na⁺ ratios >100. A single aspartic residue in the pore region of TRPV5 and TRPV6 is critical for Ca²⁺ permeation which is completely abolished after replacement of this aspartate residue by alanine.

Function of TRPV6 Membrane Protein

The TRPV5 and TRPV6 channels are both parts of transcellular Ca²⁺ transport in epithelial cells. Presumably, Ca²⁺ enters the epithelial cells via TRPV5 and TRPV6 at the apical membrane along the electrochemical gradient. Incoming Ca²⁺ regulates TRPV5/6 channels by feedback inhibition and may reach the bloodstream via Na⁺/Ca²⁺-exchangers and plasma membrane. TRPV6 is supposed to be responsible for Ca²⁺ uptake in the intestine. The intact TRPV6 channel is also an essential component for the Ca²⁺ uptake by the epididymal epithelium. TRPV6 is important for normal Ca²⁺ ion homeostasis in the body, including bone and skin. The channel is activated by low internal calcium level, probably including intracellular calcium store depletion, and the current exhibits an inward rectification. Several studies have demonstrated that TRPV6 is over-expressed and promotes the proliferation and invasion in many cancers, such as prostate cancer, breast and colon cancer. The contribution to carcinogenesis is unclear. However, TRPV6 can serve as a marker for cancer detection and progression and may be useful as a target for therapeutic strategies.

Fig.1 Integrated model of active epithelial Ca²⁺ transport. (Schoeber, 2007)

Application of TRPV6 Membrane Protein in Literature

1. Skrzypski M., et al. TRPV6 channel modulates proliferation of insulin secreting INS-1E beta cell line. Biochim Biophys Acta. 2015, 1853(12):3202-10. PubMed ID: 26384871
   
   

   This article demonstrates for the first time the expression of TRPV6 in INS-1E cells and rat pancreatic beta cells and describes its role in modulating calcium signaling, beta cell proliferation, and insulin mRNA expression. In contrast, TRPV6 fails to influence insulin secretion.

2. Vachel L., et al. The low PLC-δ1 expression in cystic fibrosis bronchial epithelial cells induces upregulation of TRPV6 channel activity. Cell Calcium. 2015, 57(1):38-48. PubMed ID: 25477137
   
   

   This article suggests that TRPV6 and PLC-δ1 can be regarded as critical actors of Ca(2+) homeostasis in CF human bronchial epithelial cells.

3. Sun F., et al. TRPV6 is a prognostic marker in early-stage cervical squamous cell carcinoma. Tumor Biology. 2016. PubMed ID: 27747588
   
   

   This article suggests that the expression of TRPV6 is downregulated in early-stage CSCC tissues. Multivariate analyses show that TRPV6 is an independent prognostic factor for survival in early-stage CSCC patients, especially in FIGO stage I patients. Thus, TRPV6 may serve as a novel prognostic biomarker for early-stage CSCC patients.

4. Chen F., et al. Knockout of TRPV6 causes osteopenia in mice by increasing osteoclastic differentiation and activity. Cellular Physiology and Biochemistry. 2014, 33(3):796-809. PubMed ID: 24686448
   
   

   This article reveals that TRPV6 plays an essential role in bone metabolism and is a critical regulator in osteoclasts differentiation and bone resorption.

5. Zhang S.S., et al. TRPV6 plays a new role in predicting survival of patients with esophageal squamous cell carcinoma. Diagnostic Pathology. 2016, 11:14. PubMed ID: 26818094
   
   

   This article suggests that TRPV6 is down-regulated in ESCC. As a predictive biomarker, TRPV6 plays a Janus-like role in predicting survival of male and female ESCC patients.

TRPV6 Preparation Options

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• Magic™ Membrane Protein Production Platform
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During the past years, Creative Biolabs has successfully generated many functional membrane proteins for our global customers. We are happy to accelerate the development of our clients’ programs with our one-stop, custom-oriented service. For more detailed information, please feel free to contact us.

Reference

1. Schoeber J P, et al. (2007). Concerted action of associated proteins in the regulation of TRPV5 and TRPV6. Biochemical Society Transactions. 35(Pt 1):115-9.

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