TRPV5 Membrane Protein Introduction

Introduction of TRPV5

TRPV5 belongs to the TRP superfamily, which consists of cation-selective ion channels with similar molecular structures. The TRPV5 gene consists of 15 exons, which translates into a protein of 729 amino acids in human. This protein contains six putative transmembrane domains and an intracellular N and C tail. Functional TRPV5 channels exist as tetramers forming together a single Ca²⁺-selective pore. The pore is formed by the hydrophobic region between TM5 and TM6. The pore-residue aspartate-542 appeared to be crucial for high-affinity Ca²⁺ binding and selectivity. Mutation of this aspartate into an alanine abolished Ca²⁺ permeation, whereas the current carried by monovalent cations remained intact. The channel is activated by low internal calcium level and the current exhibits an inward rectification. A Ca²⁺-dependent feedback regulation includes fast channel inactivation and slow current decay. TRPV5 is expressed in kidney, duodenum, jejunum, placenta and pancreas.

Function of TRPV5 Membrane Protein

As a Ca²⁺ channel, TRPV-5 contributes to maintaining the homeostasis of the human skeleton via a negative feedback loop in receptor activator of NF-κB ligand (RANKL)-induced bone resorption. Furthermore, analysis of femoral bone sections from TRPV5 knockout (TRPV5^-/-) mice revealed increased osteoclast numbers and osteoclast area. Therefore, TRPV5 is essential for osteoclast differentiation and bone resorption. TRPV5 has also been confirmed to be involved in the estrogen-mediated Ca²⁺ influx in many cells. It has been demonstrated that TRPV5 protein expression is highly modulated by estrogen in the kidney. Furthermore, estrogen has the ability to regulate renal Ca²⁺ re-absorption through rapid effects on TRPV5 channel activity in kidney and intestine, which is required for normal Ca²⁺ reabsorption in the kidney distal convoluted tubules.

Fig.1 Models of the regulation of apical membrane TRPV5 in renal distal tubules by Klotho and FGF23. (Andrukhova, 2014)

Application of TRPV5 Membrane Protein in Literature

1. Na T. and Peng J.B. TRPV5: a Ca(2+) channel for the fine-tuning of Ca(2+) reabsorption. Handb Exp Pharmacol. 2014, 222:321-57. PubMed ID: 24756712
   
   

   This article finds that TRPV5 represents a potential therapeutic target for disorders with altered Ca(2+) homeostasis.

2. van der Hagen E.A., et al. Coordinated regulation of TRPV5-mediated Ca²⁺ transport in primary distal convolution cultures. Pflugers Arch. 2014, 466(11):2077-87. PubMed ID: 24557712
   
   

   This article shows that a novel primary cell model with TRPV5-dependent Ca(2+) transport characteristics is successfully established, enabling comprehensive studies of transcellular Ca(2+) transport.

3. Tomilin V.N., et al. TRPV5/V6 Channels Mediate Ca(2+) Influx in Jurkat T Cells Under the Control of Extracellular pH. Journal of Cellular Biochemistry. 2016, 117(1):197-206. PubMed ID: 26096460
   
   

   This article suggests that strong environmental cues may affect the intracellular calcium level in Jurkat T cells by influencing the traffic of TRPV5/V6 channels in lymphocytes.

4. Fan H., et al. Expression and prognostic roles of TRPV5 and TRPV6 in non-small cell lung cancer after curative resection. Asian Pacific Journal of Cancer Prevention. 2014,15(6):2559-63. PubMed ID: 24761864
   
   

   This article reveals that the combined expression of TRPV5 and TRPV6 in tumor tissues presents promising prognostic value in NSCLC patients.

5. Chen F., et al. Estrogen inhibits RANKL-induced osteoclastic differentiation by increasing the expression of TRPV5 channel. Journal of Cellular Biochemistry. 2014, 115(4):651-8. PubMed ID: 24150765
   
   

   This article suggests that TRPV5 may contribute to the process of estrogen-inhibited osteoclastogenesis and bone resorption activity.

TRPV5 Preparation Options

Membrane protein studies have advanced significantly over the past few years. Based on our versatile Magic™ membrane protein production platform, we could offer a series of membrane protein preparation services for worldwide customers in reconstitution forms as well as multiple active formats. Aided by our versatile Magic™ anti-membrane protein antibody discovery platform, we also provide customized anti-TRPV5 antibody development services.

• 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. Andrukhova O, et al. (2014). FGF23 promotes renal calcium reabsorption through the TRPV5 channel. EMBO Journal. 33(3):229-46.

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