Transient receptor potential cation channel subfamily V member 4 is an ion channel protein that in humans is encoded by the ''TRPV4''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. The ''TRPV4'' gene encodes TRPV4, initially named "vanilloid-receptor related osmotically activated channel" (VR-OAC) and "OSM9-like

transient receptor potential Transient receptor potential channels (TRP channels) are a group of ion channels located mostly on the plasma membrane of numerous animal cell types. Most of these are grouped into two broad groups: Group 1 includes TRPC ( "C" for canonical), TRP ...

channel, member 4 (OTRPC4)", a member of the vanilloid subfamily in the

(TRP) superfamily of

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...

s. The encoded protein is a Ca²⁺-permeable, nonselective cation channel that has been found involved in multiple physiologic functions, dysfunctions and also disease. It functions in the regulation of systemic osmotic pressure by the brain, in vascular function, in liver, intestinal, renal and bladder function, in skin barrier function and response of the skin to ultraviolet-B radiation, in growth and structural integrity of the skeleton, in function of joints, in airway- and lung function, in retinal and inner ear function, and in pain. The channel is activated by osmotic, mechanical and chemical cues. It also responds to thermal changes (warmth). Channel activation can be sensitized by inflammation and injury. The ''TRPV4'' gene has been co-discovered by W. Liedtke et al. and R. Strotmann et al.

Clinical significance

Channelopathy

mutation In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, ...

s in the ''TRPV4'' gene lead to skeletal dysplasias, premature osteoarthritis, and neurological motor function disorders and are associated with a range of disorders, including brachyolmia type 3,

congenital distal spinal muscular atrophy Congenital distal spinal muscular atrophy (cDSMA), also known as distal hereditary motor neuropathy (or neuronopathy) type VIII (dHMN8), is a Heredity, hereditary medical condition characterized by muscle wasting (atrophy), particularly of Anato ...

, Familial digital arthropathy-brachydactyly (FDAB), scapuloperoneal spinal muscular atrophy, and subtype 2C of

Charcot–Marie–Tooth disease Charcot-Marie-Tooth disease (CMT) is an inherited neurological disorder that affects the peripheral nerves responsible for transmitting signals between the brain, spinal cord, and the rest of the body. This is the most common inherited neuropath ...

Pharmacology

A number of TRPV4 agonists and antagonists have been identified since its discovery. The discovery of unselective modulators (e.g. antagonist ruthenium red) was followed by the apparition of more potent (agonist 4aPDD) or selective (antagonist RN-1734) compounds, including some with bioavailability suitable for in vivo pharmacology studies such as agonist GSK1016790A (with ~10 fold selectivity vs TRPV1), and antagonists HC-067047 (with ~5 fold selectivity vs hERG and ~10 fold selectivity vs TRPM8) and RN-9893 (with ~50 fold selectivity vs TRPM8 and ~10 fold selectivity vs M1). Resolvin D1 (RvD1), a metabolite of the

omega 3 fatty acid Omega−3 fatty acids, also called omega−3 oils, ω−3 fatty acids or ''n''−3 fatty acids, are polyunsaturated fatty acids (PUFAs) characterized by the presence of a double bond three atoms away from the terminal methyl group in their c ...

docosahexaenoic acid Docosahexaenoic acid (DHA) is an omega−3 fatty acid that is an important component of the human brain, cerebral cortex, skin, and retina. It is given the fatty acid notation 22:6(''n''−3). It can be synthesized from alpha-linolenic acid or ...

, is a member of the

specialized proresolving mediators Specialization or Specialized may refer to: Academia * Academic specialization, may be a course of study or major at an academic institution or may refer to the field in which a specialist practices * Specialty (medicine), a branch of medical ...

(SPMs) class of metabolites that function to resolve diverse inflammatory reactions and diseases in animal models and, it is proposed, humans. This SPM also dampens pain perception arising from various inflammation-based causes in animal models. The mechanism behind this pain-dampening effect involves the inhibition of TRPV4, probably (in at least certain cases) by an indirect effect wherein it activates another receptor located on neurons or nearby

microglia Microglia are a type of glia, glial cell located throughout the brain and spinal cord of the central nervous system (CNS). Microglia account for about around 5–10% of cells found within the brain. As the resident macrophage cells, they act as t ...

astrocyte Astrocytes (from Ancient Greek , , "star" and , , "cavity", "cell"), also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord. They perform many functions, including biochemical control of en ...

s. CMKLR1,

GPR32 G protein-coupled receptor 32, also known as GPR32 or the RvD1 receptor, is a human receptor (biochemistry) belonging to the rhodopsin-like subfamily of G protein-coupled receptors. Gene The ''GPR32'' was initially identified and defined by mo ...

, FPR2, and

NMDA receptor The ''N''-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and predominantly Ca2+ ion channel found in neurons. The NMDA receptor is one of three types of ionotropic glutamate receptors, the other ...

s have been proposed to be the receptors through which a SPM may operate to down-regulate TRPs and thereby pain perception.

Interactions

TRPV4 has been shown to interact with

MAP7 Ensconsin is a protein that in humans is encoded by the ''MAP7'' gene. Function The product of this gene is a microtubule-associated protein In cell biology, microtubule-associated proteins (MAPs) are proteins that interact with the microtu ...

and LYN.

Implication in Temperature-Dependent Sex Determination in Reptiles

TRPV4 has been proposed to be the thermal sensor in gonads of '' Alligator mississipiensis'', a species with

temperature-dependent sex determination Temperature-dependent sex determination (TSD) is a type of environmental sex determination in which the temperatures experienced during embryonic/larval development determine the sex of the offspring. It is observed in reptiles and teleost fish, ...

. However the data were over interpreted and TRPV4 is probably not involved in temperature-dependent sex determination due to large overlap of expression at male producing temperature and female producing temperature for example.

References

External links