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.
|Basic Information of TRPV4|
|Protein Name||Transient receptor potential cation channel subfamily V member 4|
|Gene Name||TRPV4, VRL2, VROAC|
|Aliases||Osm-9-like TRP channel 4 (OTRPC4), Transient receptor potential protein 12 (TRP12), Vanilloid receptor-like channel 2, Vanilloid receptor-like protein 2 (VRL-2), Vanilloid receptor-related osmotically-activated channel (VR-OAC)|
|Organism||Homo sapiens (Human)|
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)
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.
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.
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.
This article reveals that the therapeutic potential of TRPV4 inhibitors can be systematically examined in a variety of lung diseases.
This article suggests that TRPV4 activity mediates pulmonary fibrogenesis and manipulation of TRPV4 channel activity has potential as a therapeutic approach for fibrotic diseases.
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