TRPV4 Membrane Protein Introduction

Introduction of TRPV4

A full-length TRPV4 monomer which consists of 871 amino acids and similar to all TRP channels, has 6 transmembrane domains. Aothough TRPV4 preferentially transports Ca²⁺ and Mg²⁺, unlike TRPV5 and TRPV6, TRPV4 is only weakly selective for divalent cations. TRPV4 is almost ubiquitously expressed and can be found in the brain, lung, heart, vasculature, kidney, bladder, skin, liver, and bone, among other organs. In the lung, TRPV4 has been identified in vascular smooth muscle, endothelial cells, and epithelial cells of the alveoli, trachea, and bronchi. Additionally, TRPV4 is highly expressed in several immune cell types that reside in, and play important roles in, lung function, including macrophages and neutrophils. Sensitization is the augmentation of the TRPV4 response to subsequent stimulation by a direct agonist. Whereas opening of TRPV4 by intracellular signaling does not require exogenous agonist.TRPV4 is activated by endogenous ligands such as the EET’s and by signaling through phosphorylation of TRPV4.

Function of TRPV4 Membrane Protein

TRPV4 is abundant in the vascular endothelium but is also found in the smooth muscle of pulmonary, aortic and cerebral arteries where it is thought to mediate vascular tone. TRPV4 is a key regulator of neuronal function in specific regions of the peripheral and the central nervous system. TRPV4 senses temperature in the hypothalamus to modulate the excitability of dopaminergic neurons of the substania nigra at physiological temperatures and regulating a population of serotonergic neurons in the brainstem thermo afferent pathway which modulates physiology and behavior. In the hippocampus, TRPV4 is active above 37°C (98.6°F) and regulates the expression of TRPV4 in neuronal excitability astrocytes, where its activity increases post-ischemia and hypoxia and plays a role in oxidative stress-induced cell death relevant to stroke. TRPV4 is expressed in sensory neurons of the dorsal root and trigeminal ganglia and plays a role in pain sensation. Finally, it is critical that several TRPV4 gene mutations are associated with a variety of skeletal and neurological disease entities. TRPV4-associated skeletal dysplasia includes various forms of dwarfism that have been causally linked to the channel mutation. Furthermore, TRPV4 mutations have been found to cause several motor sensory neuropathies related to CharcotMarie-Tooth syndrome.

Fig.1 Proposed model for the local control of TRPV4 channels in arterial myocytes. (Mercado, 2014)

Application of TRPV4 Membrane Protein in Literature

1. McNulty A.L., et al. TRPV4 as a therapeutic target for joint diseases. Naunyn Schmiedebergs Arch Pharmacol. 2015,388(4):437-50. PubMed ID: 25519495
   
   

   This article finds that TRPV4 plays a key role in transducing mechanical, pain, and inflammatory signals within joint tissues and thus is an attractive therapeutic target to modulate the effects of joint diseases.

2. Goldenberg N.M., et al. TRPV4 Is Required for Hypoxic Pulmonary Vasoconstriction. Anesthesiology. 2015, 122(6):1338-48. PubMed ID: 25815455
   
   

   This article finds the interaction between TRPV4 and TRPC6 in pulmonary artery smooth muscle cell (PASMC) remains unaltered during hypoxia and further suggests that both channels form heteromeric at baseline in PASMC and become recruited to caveolae (and presumably, activated) conjointly upon exposure to hypoxia.

3. Saifeddine M., et al. GPCR-mediated EGF receptor transactivation regulates TRPV4 action in the vasculature. British Journal of Pharmacology. 2014, 64(4):547-56. PubMed ID: 24266897
   
   

   This article suggests that GPCR potentiation of TRPV4 action and TRPV4-dependent Tx receptor activation are important regulators of vascular function and could be therapeutically targeted in vascular diseases.

4. Goldenberg N.M., et al. TRPV4: physiological role and therapeutic potential in respiratory diseases. Naunyn Schmiedebergs Arch Pharmacol. 2015, 388(4):421-36. PubMed ID: 25342095
   
   

   This article reveals that the therapeutic potential of TRPV4 inhibitors can be systematically examined in a variety of lung diseases.

5. Rahaman S.O., et al. TRPV4 mediates myofibroblast differentiation and pulmonary fibrosis in mice. Journal of Clinical Investegation. 2014, 124(12):5225-38. PubMed ID: 25365224
   
   

   This article suggests that TRPV4 activity mediates pulmonary fibrogenesis and manipulation of TRPV4 channel activity has potential as a therapeutic approach for fibrotic diseases.

TRPV4 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-TRPV4 antibody development services.

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

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. Mercado J, et al. (2014). Local control of TRPV4 channels by AKAP150-targeted PKC in arterial smooth muscle. Journal of General Physiology. 143 (5): 559.

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