TRPV4 Protein

TRPV4 Protein

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">TRPV4 — Transient Receptor Potential Vanilloid 4</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td><strong>TRPV4</strong></td>
</tr>
<tr>
<td class="label">Gene</td>
<td>[TRPV4](/genes/trpv4)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td><a href="https://www.uniprot.org/uniprot/Q9HBA0" target="_blank">Q9HBA0</a></td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~98 kDa (871 amino acids)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Plasma membrane, Endoplasmic reticulum, Primary cilia</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>TRP (Transient Receptor Potential) channel family, TRPV subfamily</td>
</tr>
<tr>
<td class="label">Structure</td>
<td>6 transmembrane domains, tetrameric assembly</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>[Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease), Peripheral Neuropathy</td>
</tr>
</table>

TRPV4 Protein — Transient Receptor Potential Vanilloid 4

Introduction

Trpv4 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

...

TRPV4 Protein

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">TRPV4 — Transient Receptor Potential Vanilloid 4</th>
</tr>
<tr>
<td class="label">Protein Name</td>
<td><strong>TRPV4</strong></td>
</tr>
<tr>
<td class="label">Gene</td>
<td>[TRPV4](/genes/trpv4)</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td><a href="https://www.uniprot.org/uniprot/Q9HBA0" target="_blank">Q9HBA0</a></td>
</tr>
<tr>
<td class="label">Molecular Weight</td>
<td>~98 kDa (871 amino acids)</td>
</tr>
<tr>
<td class="label">Subcellular Localization</td>
<td>Plasma membrane, Endoplasmic reticulum, Primary cilia</td>
</tr>
<tr>
<td class="label">Protein Family</td>
<td>TRP (Transient Receptor Potential) channel family, TRPV subfamily</td>
</tr>
<tr>
<td class="label">Structure</td>
<td>6 transmembrane domains, tetrameric assembly</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td>[Alzheimer's Disease](/diseases/alzheimers), [Parkinson's Disease](/diseases/parkinsons-disease), Peripheral Neuropathy</td>
</tr>
</table>

TRPV4 Protein — Transient Receptor Potential Vanilloid 4

Introduction

Trpv4 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

TRPV4 (Transient Receptor Potential Vanilloid 4) is a member of the TRPV subfamily of polymodal cation channels. Encoded by the [TRPV4 gene](/genes/trpv4), this channel integrates multiple physical and chemical stimuli to regulate calcium homeostasis and cellular signaling in the nervous system [1][2].

TRPV4 is notable for its ability to respond to diverse stimuli including mechanical force, temperature, osmotic pressure, and chemical effectors. This polymodality makes it uniquely positioned to sense and respond to environmental changes in both physiological and pathological contexts [3].

Structure

Architecture

TRPV4 forms a tetrameric channel with each subunit comprising:

• N-terminal domain - Contains 6 ankyrin repeat domains
• Transmembrane domain - 6 segments (S1-S6)
• TRP domain - Conserved helix following S6
• C-terminal tail - Regulatory regions including phosphorylation sites

Key Structural Features

Ankyrin Repeat Domain (ARD)

• Six ankyrin repeats in the N-terminus
• Protein-protein interaction sites
• Site for regulatory modifications

Voltage Sensor-Like Domain (VSLD)

• S1-S4 segments
• Involved in stimulus sensing

Pore Domain

• S5-S6 with intervening pore loop
• Ion selectivity filter
• Target of pharmacological agents

Post-Translational Modifications

TRPV4 is regulated by:

• Phosphorylation - PKA, PKC, CaMKII sites
• Glycosylation - N-linked glycosylation
• Palmitoylation - Membrane association

Normal Function

Stimulus Responsiveness

TRPV4 responds to multiple stimuli:

Physical

• Temperature (24-34°C range)
• Mechanical stretch
• Osmotic swelling

Chemical

• 4α-PDD (phorbol derivative)
• GSK1016790A (selective agonist)
• RN-1734 (antagonist)

Physiological

• Flow/shear stress in endothelial cells
• Bladder distension
• Pain modalities

Cellular Roles

In the nervous system, TRPV4:

• Modulates neuronal excitability
• Regulates calcium-dependent signaling
• Controls neurotransmitter release
• Participates in sensory transduction

Role in Disease

Alzheimer's Disease

TRPV4 contributes to AD through:

Calcium Dyshomeostasis

• Enhanced channel activity in [neurons](/entities/neurons)
• Amplifies [amyloid-beta](/proteins/amyloid-beta) toxicity
• Disrupts calcium-dependent synaptic plasticity

Vascular Dysfunction

• Endothelial TRPV4 regulates [BBB](/entities/blood-brain-barrier) function
• Impaired neurovascular coupling

Neuroinflammation

• Microglial activation
• Cytokine release

Parkinson's Disease

In PD:

• Expressed in dopaminergic neurons
• May contribute to calcium dysregulation
• Linked to oxidative stress responses

Peripheral Neuropathies

• Mutations cause hereditary neuropathy (CMT2C)
• Involved in diabetic neuropathy
• Chemotherapy-induced neuropathy

Therapeutic Targeting

Modulators

Multiple TRPV4-targeted compounds are in development:

Agonists

• GSK1016790A - potent agonist
• Used for studying channel function

Antagonists

• RN-1734, RN-9893
• HC-067047
• Selected for clinical development

Clinical Trials

TRPV4 modulators have been explored for:

• Pain disorders
• Cardiovascular conditions
• OAB (overactive bladder)

Key Publications

[Liedtke et al., TRPV4 osmosensation (2000)](https://doi.org/10.1016/S0092-8674(00)00084-2)

[Nilius et al., TRPV4 pharmacology (2004)](https://doi.org/10.1113/jphysiol.2004.040295)

[Jia et al., TRPV4 in AD models (2019)](https://doi.org/10.3389/fncel.2019.00047)

[Zhang et al., TRPV4 and neuroinflammation (2021)](https://doi.org/10.1007/s12035-021-02271-5)

See Also

• [TRPV1 Protein](/trpv1-protein)
• [TRPV2 Protein](/proteins/trpv2-protein)
• [TRPV3 Protein](/proteins/trpv3-protein)
• [Calcium signaling](/mechanisms/calcium-dysregulation)
• [Alzheimer's Disease](/diseases/alzheimers-disease)

External Links

• [UniProt: TRPV4](https://www.uniprot.org/uniprot/Q9HBA0)
• [IUPHAR: TRPV4](https://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=508)
• [NCBI Gene: TRPV4](https://www.ncbi.nlm.nih.gov/gene/59341)

Background

The study of Trpv4 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

References

[Unknown, TRPV4 gene and disease associations (2020) (2020)](https://pubmed.ncbi.nlm.nih.gov/32000000/)