scholarly journals Functional coupling between TRPV4 channel and TMEM16F modulates human trophoblast fusion

2021 ◽  
Author(s):  
Yang Zhang ◽  
Pengfei Liang ◽  
Ke Zoe Shan ◽  
Liping Feng ◽  
Yong Chen ◽  
...  
Keyword(s):  
Cell Fusion ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Functional Expression ◽  
Activation Mechanism ◽  
Functional Coupling ◽  
Transient Receptor Potential Vanilloid ◽  
Human Trophoblast ◽  
Phospholipid Scramblase ◽  
Transient Receptor

TMEM16F, a Ca2+-activated phospholipid scramblase (CaPLSase), is critical for placental trophoblast syncytialization, HIV infection, and SARS-CoV2-mediated syncytialization. How TMEM16F is activated during cell fusion is unclear. Here, we used trophoblasts as a model for cell fusion and demonstrated that Ca2+ influx through Ca2+ permeable transient receptor potential vanilloid channel TRPV4 is critical for TMEM16F activation and subsequent human trophoblast fusion. GSK1016790A, a TRPV4 specific agonist, robustly activates TMEM16F in trophoblasts. Patch-clamp electrophysiology demonstrated that TRPV4 and TMEM16F are functionally coupled within Ca2+ microdomains in human trophoblasts. Pharmacological inhibition or gene silencing of TRPV4 hindered TMEM16F activation and subsequent trophoblast syncytialization. Our study uncovers the functional expression of TRPV4 and a physiological activation mechanism of TMEM16F in human trophoblasts, thus providing us with novel strategies to regulate CaPLSase activity as a critical checkpoint of physiologically- and disease-relevant cell fusion events.

Transient Receptor Potential Vanilloid 4 and Serum Glucocorticoid–regulated Kinase 1 Are Critical Mediators of Lung Injury in Overventilated Mice In Vivo

2017 ◽  
Vol 126 (2) ◽  
pp. 300-311 ◽  
Author(s):  
Laura Michalick ◽  
Lasti Erfinanda ◽  
Ulrike Weichelt ◽  
Markus van der Giet ◽  
Wolfgang Liedtke ◽  
...  
Keyword(s):  
Lung Injury ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Cyclic Stretch ◽  
Proximity Ligation Assay ◽  
Functional Coupling ◽  
Transient Receptor Potential Vanilloid ◽  
Ventilator Induced Lung Injury ◽  
Barrier Failure ◽  
Transient Receptor

Abstract Background Mechanical ventilation can cause lung endothelial barrier failure and inflammation cumulating in ventilator-induced lung injury. Yet, underlying mechanotransduction mechanisms remain unclear. Here, the authors tested the hypothesis that activation of the mechanosensitive Ca2+ channel transient receptor potential vanilloid (TRPV4) by serum glucocorticoid–regulated kinase (SGK) 1 may drive the development of ventilator-induced lung injury. Methods Mice (total n = 54) were ventilated for 2 h with low (7 ml/kg) or high (20 ml/kg) tidal volumes and assessed for signs of ventilator-induced lung injury. Isolated-perfused lungs were inflated with continuous positive airway pressures of 5 or 15 cm H2O (n = 7 each), and endothelial calcium concentration was quantified by real-time imaging. Results Genetic deficiency or pharmacologic inhibition of TRPV4 or SGK1 protected mice from overventilation-induced vascular leakage (reduction in alveolar protein concentration from 0.84 ± 0.18 [mean ± SD] to 0.46 ± 0.16 mg/ml by TRPV4 antagonization), reduced lung inflammation (macrophage inflammatory protein 2 levels of 193 ± 163 in Trpv4−/−vs. 544 ± 358 pmol/ml in wild-type mice), and attenuated endothelial calcium responses to lung overdistension. Functional coupling of TRPV4 and SGK1 in lung endothelial mechanotransduction was confirmed by proximity ligation assay demonstrating enhanced TRPV4 phosphorylation at serine 824 at 18% as compared to 5% cyclic stretch, which was prevented by SGK1 inhibition. Conclusions Lung overventilation promotes endothelial calcium influx and barrier failure through a mechanism that involves activation of TRPV4, presumably due to phosphorylation at its serine 824 residue by SGK1. TRPV4 and SGK1 may present promising new targets for prevention or treatment of ventilator-induced lung injury.

Functional Expression of an Osmosensitive Cation Channel, Transient Receptor Potential Vanilloid 4, in Rat Vestibular Ganglia

2016 ◽  
Vol 21 (4) ◽  
pp. 268-274 ◽  
Author(s):  
Takefumi Kamakura ◽  
Makoto Kondo ◽  
Yoshihisa Koyama ◽  
Yukiko Hanada ◽  
Yusuke Ishida ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Functional Expression ◽  
Ruthenium Red ◽  
Cation Channel ◽  
Trigeminal Ganglia ◽  
Transient Receptor Potential Vanilloid ◽  
Trpv Channels ◽  
Polymerase Chain ◽  
Transient Receptor

Transient receptor potential vanilloid (TRPV) 4 is a nonselective cation channel expressed in sensory neurons such as those in the dorsal root and trigeminal ganglia, kidney, and inner ear. TRPV4 is activated by mechanical stress, heat, low osmotic pressure, low pH, and phorbol derivatives such as 4α-phorbol 12,13-didecanoate (4α-PDD). We investigated the expression of TRPV4 in rat vestibular ganglion (VG) neurons. The TRPV4 gene was successfully amplified from VG neuron mRNA using reverse-transcription polymerase chain reaction. Furthermore, immunoblotting showed positive expression of TRPV4 protein in VG neurons. Immunohistochemistry indicated that TRPV4 was localized predominantly on the plasma membrane of VG neurons. Calcium (Ca2+) imaging of VG neurons showed that 4α-PDD and/or hypotonic stimuli caused an increase in intracellular Ca2+ concentration ([Ca2+]i) that was almost completely inhibited by ruthenium red, a selective antagonist of TRPV channels. Interestingly, a [Ca2+]i increase was evoked by both hypotonic stimuli and 4α-PDD in approximately 38% of VG neurons. These data indicate that TRPV4 is functionally expressed in VG neurons as an ion channel and that TRPV4 likely participates in VG neurons for vestibular neurotransmission as an osmoreceptor and/or mechanoreceptor.

scholarly journals A TRPV2–PKA Signaling Module for Transduction of Physical Stimuli in Mast Cells

2004 ◽  
Vol 200 (2) ◽  
pp. 137-147 ◽  
Author(s):  
Alexander J. Stokes ◽  
Lori M.N. Shimoda ◽  
Murielle Koblan-Huberson ◽  
Chaker N. Adra ◽  
Helen Turner
Keyword(s):  
Mast Cells ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Functional Coupling ◽  
Transient Receptor Potential Vanilloid ◽  
Functional Responses ◽  
Signaling Mechanism ◽  
Cutaneous Mast Cell ◽  
Transient Receptor

Cutaneous mast cell responses to physical (thermal, mechanical, or osmotic) stimuli underlie the pathology of physical urticarias. In vitro experiments suggest that mast cells respond directly to these stimuli, implying that a signaling mechanism couples functional responses to physical inputs in mast cells. We asked whether transient receptor potential (vanilloid) (TRPV) cation channels were present and functionally coupled to signaling pathways in mast cells, since expression of this channel subfamily confers sensitivity to thermal, osmotic, and pressure inputs. Transcripts for a range of TRPVs were detected in mast cells, and we report the expression, surface localization, and oligomerization of TRPV2 protein subunits in these cells. We describe the functional coupling of TRPV2 protein to calcium fluxes and proinflammatory degranulation events in mast cells. In addition, we describe a novel protein kinase A (PKA)–dependent signaling module, containing PKA and a putative A kinase adapter protein, Acyl CoA binding domain protein (ACBD)3, that interacts with TRPV2 in mast cells. We propose that regulated phosphorylation by PKA may be a common pathway for TRPV modulation.

scholarly journals Interaction between TRPV1-expressing neurons in the hypothalamus

2019 ◽  
Vol 121 (1) ◽  
pp. 140-151 ◽  
Author(s):  
Adrien J. R. Molinas ◽  
Lucie D. Desmoulins ◽  
Brooke V. Hamling ◽  
Sierra M. Butcher ◽  
Imran J. Anwar ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Direct Interaction ◽  
Receptor Potential ◽  
Functional Expression ◽  
Hypothalamic Nucleus ◽  
Transient Receptor Potential Vanilloid ◽  
Adult Mice ◽  
Hypothalamic Nuclei ◽  
Transient Receptor

Transient receptor potential vanilloid type 1 (TRPV1) is a ligand-gated ion channel expressed in the peripheral and central nervous systems. TRPV1-dependent mechanisms take part in a wide range of physiological and pathophysiological pathways including the regulation of homeostatic functions. TRPV1 expression in the hypothalamus has been described as well as evidence that TRPV1-dependent excitatory inputs to hypothalamic preautonomic neurons are diminished in diabetic conditions. Here we aimed to determine the functional expression of TRPV1 in two hypothalamic nuclei known to be involved in the central control of metabolism and to test the hypothesis that TRPV1-expressing neurons receive TRPV1-expressing inputs. A mouse model (TRPV1Cre/tdTom) was generated to identify TRPV1-expressing cells and determine the cellular properties of TRPV1-expressing neurons in adult mice. Our study demonstrated the functional expression of TRPV1 in the dorsomedial hypothalamic nucleus and paraventricular nucleus in adult mice. Our findings revealed that a subset of TRPV1Cre/tdTom neurons receive TRPV1-expressing excitatory inputs, indicating direct interaction between TRPV1-expressing neurons. In addition, astrocytes likely play a role in the modulation of TRPV1-expressing neurons. In summary, this study identified specific hypothalamic regions where TRPV1 is expressed and functional in adult mice and the existence of direct connections between TRPV1Cre/tdTom neurons. NEW & NOTEWORTHY Transient receptor potential vanilloid type 1 (TRPV1) is expressed in the hypothalamus, and TRPV1-dependent regulation of preautonomic neurons is decreased in hyperglycemic conditions. Our study demonstrated functional expression of TRPV1 in two hypothalamic nuclei involved in the control of energy homeostasis. Our results also revealed that a subset of TRPV1-expressing neurons receive TRPV1-expressing excitatory inputs. These findings suggest direct interaction between TRPV1-expressing neurons.

scholarly journals Simultaneous Deletion of Transient Receptor Potential Vanilloid 3 and Cacna1h Undermines Ca2+ Homeostasis in Oocytes and Fertility in Mice

2018 ◽  
Author(s):  
Aujan Mehregan ◽  
Goli Ardestani ◽  
Ingrid Carvacho ◽  
Rafael Fissore
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Functional Expression ◽  
Egg Activation ◽  
Transient Receptor Potential Vanilloid ◽  
Double Knockout ◽  
Knock Out ◽  
Transient Receptor ◽  
Mammalian Eggs ◽  
Channel Currents

In mammals, calcium (Ca2+) influx fills the endoplasmic reticulum, from where Ca2+ is released following fertilization to induce egg activation. However, an incomplete index of the plasma membrane channels and their specific contributions that underlie this influx in oocytes and eggs led us to simultaneously knock out the transient receptor potential vanilloid, member 3 (TRPV3) channel and the T-type channel, CaV3.2. Double knockout (dKO) females displayed subfertility and their oocytes and eggs showed significantly diminished Ca2+ store content and oscillations after fertilization compared to controls. We also found that the cell cycle stage during maturation determines the functional expression of channels whereby they show a distinct permeability to certain ions. In total, we demonstrate that TRPV3 and CaV3.2 are required for initiating physiological oscillations and that Ca2+ influx dictates the periodicity of oscillations during fertilization. dKO gametes will be indispensable to identify the complete native channel currents present in mammalian eggs.

scholarly journals Increased TRPV4 expression in non-myelinating Schwann cells is associated with demyelination after sciatic nerve injury

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Xiaona Feng ◽  
Yasunori Takayama ◽  
Nobuhiko Ohno ◽  
Hirosato Kanda ◽  
Yi Dai ◽  
...  
Keyword(s):  
Nervous System ◽  
Sciatic Nerve ◽  
Schwann Cells ◽  
Nerve Injury ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Functional Expression ◽  
Transient Receptor Potential Vanilloid ◽  
Sciatic Nerves ◽  
Transient Receptor

AbstractTransient receptor potential vanilloid 4 (TRPV4) is a non-selective calcium-permeable cation channel that is widely expressed and activated in various neurons and glial cells in the nervous system. Schwann cells (SCs) are primary glia cells that wrap around axons to form the myelin sheath in the peripheral nervous system. However, whether TRPV4 is expressed and functions in SCs is unclear. Here, we demonstrate functional expression of TRPV4 in mouse SCs and investigated its physiological significance. Deletion of TRPV4 did not affect normal myelin development for SCs in sciatic nerves in mice. However, after sciatic nerve cut injury, TRPV4 expression levels were remarkably increased in SCs following nerve demyelination. Ablation of TRPV4 expression impaired the demyelinating process after nerve injury, resulting in delayed remyelination and functional recovery of sciatic nerves. These results suggest that local activation of TRPV4 could be an attractive pharmacological target for therapeutic intervention after peripheral nerve injury.

Functional expression of transient receptor potential vanilloid 4 in the mouse cochlea

Neuroreport ◽  
2006 ◽  
Vol 17 (2) ◽  
pp. 135-139 ◽  
Author(s):  
Jing Shen ◽  
Narinobu Harada ◽  
Nobuo Kubo ◽  
Bing Liu ◽  
Atsuko Mizuno ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Functional Expression ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor
Sign in / Sign up

Export Citation Format

Share Document