scholarly journals Molecular mapping of transmembrane mechanotransduction through the β1 integrin–CD98hc–TRPV4 axis

2020 ◽  
Vol 133 (20) ◽  
pp. jcs248823 ◽  
Author(s):  
Ratnakar Potla ◽  
Mariko Hirano-Kobayashi ◽  
Hao Wu ◽  
Hong Chen ◽  
Akiko Mammoto ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Molecular Mapping ◽  
Calcium Influx ◽  
Focal Adhesions ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Β1 Integrin ◽  
Mechanical Forces ◽  
C Terminus ◽  
Transient Receptor

ABSTRACTOne of the most rapid (less than 4 ms) transmembrane cellular mechanotransduction events involves activation of transient receptor potential vanilloid 4 (TRPV4) ion channels by mechanical forces transmitted across cell surface β1 integrin receptors on endothelial cells, and the transmembrane solute carrier family 3 member 2 (herein denoted CD98hc, also known as SLC3A2) protein has been implicated in this response. Here, we show that β1 integrin, CD98hc and TRPV4 all tightly associate and colocalize in focal adhesions where mechanochemical conversion takes place. CD98hc knockdown inhibits TRPV4-mediated calcium influx induced by mechanical forces, but not by chemical activators, thus confirming the mechanospecificity of this signaling response. Molecular analysis reveals that forces applied to β1 integrin must be transmitted from its cytoplasmic C terminus via the CD98hc cytoplasmic tail to the ankyrin repeat domain of TRPV4 in order to produce ultrarapid, force-induced channel activation within the focal adhesion.

scholarly journals Molecular mapping of transmembrane mechanotransduction through the β1 integrin-CD98hc-TRPV4 axis

2019 ◽  
Author(s):  
Ratnakar Potla ◽  
Mariko Hirano-Kobayashi ◽  
Hao Wu ◽  
Hong Chen ◽  
Akiko Mammoto ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Molecular Mapping ◽  
Calcium Influx ◽  
Focal Adhesions ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Β1 Integrin ◽  
Mechanical Forces ◽  
C Terminus ◽  
Transient Receptor

ABSTRACTOne of the most rapid (< 4 msec) transmembrane cellular mechanotransduction events involves activation of Transient Receptor Potential Vanilloid 4 (TRPV4) ion channels by mechanical forces transmitted across β1 integrin receptors in endothelial cells, and the transmembrane Solute Carrier family 3 member 2 (CD98hc) protein has been implicated in this response. Here, we show that β1 integrin, CD98hc, and TRPV4 all tightly associate and co-localize in focal adhesions where mechanochemical conversion takes place. CD98hc knock down inhibits TRPV4-mediated calcium influx induced by mechanical forces, but not by chemical activators, thus confirming the mechanospecificity of this signaling response. Molecular analysis revealed that forces applied to β1 integrin must be transmitted from its cytoplasmic C-terminus to the CD98hc cytoplasmic tail, and from there to the ankyrin repeat domain of TRPV4 in order to produce ultra-rapid, force-induced, channel activation within the focal adhesion.Abstract FigureGraphical abstractSUMMARYA direct path of mechanical signal transfer between β1 integrin, CD98hc, and TRPV4 channels is identified that mediates ultra-rapid transmembrane mechanochemical conversion within focal adhesions.

scholarly journals NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases

2022 ◽  
Vol 23 (2) ◽  
pp. 892
Author(s):  
Mariia Belinskaia ◽  
Tomas Zurawski ◽  
Seshu Kumar Kaza ◽  
Caren Antoniazzi ◽  
J. Oliver Dolly ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Sensory Nerves ◽  
Neonatal Rat ◽  
Transient Receptor Potential Vanilloid ◽  
C Terminus ◽  
Low Concentrations ◽  
Transient Receptor ◽  
Neuronal Functions ◽  
Differential Ability

Nerve growth factor (NGF) is known to intensify pain in various ways, so perturbing pertinent effects without negating its essential influences on neuronal functions could help the search for much-needed analgesics. Towards this goal, cultured neurons from neonatal rat trigeminal ganglia—a locus for craniofacial sensory nerves—were used to examine how NGF affects the Ca2+-dependent release of a pain mediator, calcitonin gene-related peptide (CGRP), that is triggered by activating a key signal transducer, transient receptor potential vanilloid 1 (TRPV1) with capsaicin (CAP). Measurements utilised neurons fed with or deprived of NGF for 2 days. Acute re-introduction of NGF induced Ca2+-dependent CGRP exocytosis that was inhibited by botulinum neurotoxin type A (BoNT/A) or a chimera of/E and/A (/EA), which truncated SNAP-25 (synaptosomal-associated protein with Mr = 25 k) at distinct sites. NGF additionally caused a Ca2+-independent enhancement of the neuropeptide release evoked by low concentrations (<100 nM) of CAP, but only marginally increased the peak response to ≥100 nM. Notably, BoNT/A inhibited CGRP exocytosis evoked by low but not high CAP concentrations, whereas/EA effectively reduced responses up to 1 µM CAP and inhibited to a greater extent its enhancement by NGF. In addition to establishing that sensitisation of sensory neurons to CAP by NGF is dependent on SNARE-mediated membrane fusion, insights were gleaned into the differential ability of two regions in the C-terminus of SNAP-25 (181–197 and 198–206) to support CAP-evoked Ca2+-dependent exocytosis at different intensities of stimulation.

scholarly journals Angiotensin II induces membrane trafficking of natively expressed transient receptor potential vanilloid type 4 channels in hypothalamic 4B cells

2014 ◽  
Vol 307 (8) ◽  
pp. R945-R955 ◽  
Author(s):  
Ashwini Saxena ◽  
Martha Bachelor ◽  
Yong H. Park ◽  
Flavia R. Carreno ◽  
T. Prashant Nedungadi ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Membrane Trafficking ◽  
Transient Receptor Potential ◽  
Calcium Influx ◽  
Src Kinase ◽  
Receptor Potential ◽  
Family Type ◽  
Transient Receptor Potential Vanilloid ◽  
Ang Ii ◽  
Transient Receptor

Transient receptor potential vanilloid family type 4 (TRPV4) channels are expressed in central neuroendocrine neurons and have been shown to be polymodal in other systems. We previously reported that in the rodent, a model of dilutional hyponatremia associated with hepatic cirrhosis, TRPV4 expression is increased in lipid rafts from the hypothalamus and that this effect may be angiotensin dependent. In this study, we utilized the immortalized neuroendocrine rat hypothalamic 4B cell line to more directly test the effects of angiotensin II (ANG II) on TRPV4 expression and function. Our results demonstrate the expression of corticotropin-releasing factor (CRF) transcripts, for sex-determining region Y (SRY) (male genotype), arginine vasopressin (AVP), TRPV4, and ANG II type 1a and 1b receptor in 4B cells. After a 1-h incubation in ANG II (100 nM), 4B cells showed increased TRPV4 abundance in the plasma membrane fraction, and this effect was prevented by the ANG II type 1 receptor antagonist losartan (1 μM) and by a Src kinase inhibitor PP2 (10 μM). Ratiometric calcium imaging experiments demonstrated that ANG II incubation potentiated TRPV4 agonist (GSK 1016790A, 20 nM)-induced calcium influx (control 18.4 ± 2.8% n = 5 and ANG II 80.5 ± 2.4% n = 5). This ANG II-induced increase in calcium influx was also blocked by 1 μM losartan and 10 μM PP2 (losartan 26.4 ± 3.8% n = 5 and PP2 19.7 ± 3.9% n = 5). Our data suggests that ANG II can increase TRPV4 channel membrane expression in 4B cells through its action on AT1R involving a Src kinase pathway.

Transient Receptor Potential Vanilloid 4 Dependent Calcium Influx and ATP Release in Mouse Esophageal Keratinocytes

2011 ◽  
Vol 140 (5) ◽  
pp. S-625
Author(s):  
Hiroshi Mihara ◽  
Ammar Boudaka ◽  
Toshiro Sugiyama ◽  
Yoshinori Moriyama ◽  
Makoto Tominaga
Keyword(s):  
Transient Receptor Potential ◽  
Calcium Influx ◽  
Atp Release ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor

scholarly journals Transgene-free remote magnetothermal regulation of adrenal hormones

2020 ◽  
Vol 6 (15) ◽  
pp. eaaz3734 ◽  
Author(s):  
Dekel Rosenfeld ◽  
Alexander W. Senko ◽  
Junsang Moon ◽  
Isabel Yick ◽  
Georgios Varnavides ◽  
...  
Keyword(s):  
Heat Dissipation ◽  
Transient Receptor Potential ◽  
Calcium Influx ◽  
Hormone Secretion ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Precise Control ◽  
Endogenous Expression ◽  
Transient Receptor ◽  
Electrical Signaling

The field of bioelectronic medicines seeks to modulate electrical signaling within peripheral organs, providing temporally precise control of physiological functions. This is usually accomplished with implantable devices, which are often unsuitable for interfacing with soft and highly vascularized organs. Here, we demonstrate an alternative strategy for modulating peripheral organ function, which relies on the endogenous expression of a heat-sensitive cation channel, transient receptor potential vanilloid family member 1 (TRPV1), and heat dissipation by magnetic nanoparticles (MNPs) in remotely applied alternating magnetic fields. We use this approach to wirelessly control adrenal hormone secretion in genetically intact rats. TRPV1-dependent calcium influx into the cells of adrenal cortex and medulla is sufficient to drive rapid release of corticosterone and (nor)epinephrine. As altered levels of these hormones have been correlated with mental conditions such as posttraumatic stress disorder and major depression, our approach may facilitate the investigation of physiological and psychological impacts of stress.

scholarly journals Transient receptor potential vanilloid 4-dependent calcium influx and ATP release in mouse and rat gastric epithelia

2016 ◽  
Vol 22 (24) ◽  
pp. 5512 ◽  
Author(s):  
Hiroshi Mihara ◽  
Nobuhiro Suzuki ◽  
Ammar Abdullkader Boudaka ◽  
Jibran Sualeh Muhammad ◽  
Makoto Tominaga ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Calcium Influx ◽  
Atp Release ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Transient Receptor

scholarly journals Blue Light Irradiation Induces Human Keratinocyte Cell Damage via Transient Receptor Potential Vanilloid 1 (TRPV1) Regulation

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Ju Ah. Yoo ◽  
Eunbi Yu ◽  
See-Hyoung Park ◽  
Sae Woong Oh ◽  
Kitae Kwon ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Blue Light ◽  
Transient Receptor Potential ◽  
Calcium Influx ◽  
Receptor Potential ◽  
Light Irradiation ◽  
Transient Receptor Potential Vanilloid ◽  
Skin Cells ◽  
Tnf Α ◽  
Transient Receptor

Although blue light has been reported to affect skin cells negatively, little is known about its action mechanisms in skin cells. Therefore, we investigated the role of the transient receptor potential vanilloid 1 (TRPV1) in blue light-induced effects on human keratinocytes and its underlying mechanisms. Blue light decreased cell proliferation and upregulated TRPV1 expression. Blue light also suppressed the epidermal growth factor receptor- (EGFR-) mediated signaling pathway by reducing the protein levels of EGFR and suppressing the EGFR/PI3K/AKT/GSK3β/FoxO3a pathway. The blue light-induced effect in cell proliferation was reversed by TRPV1 siRNA, but not capsazepine, a TRPV1-specific antagonist. In addition, blue light irradiation increased the production of reactive oxygen species (ROS) and tumor necrosis factor-α (TNF-α). Blue light irradiation also increased both phosphorylation levels of TRPV1 and calcium influx. The blue light-induced increase in production of ROS and TNF-α was reversed by capsazepine. Furthermore, the blue light-induced increase in production of TNF-α was attenuated by SP600125 or PDTC. These findings show that blue light regulates cell survival and production of ROS and TNF-α; its effects are mediated via TRPV1. Specifically, the effects of blue light on cell proliferation are mediated by upregulating TRPV1, a negative regulator of EGFR-FoxO3a signaling. Blue light-induced production of ROS and TNF-α is also mediated through increased calcium influx via TRPV1 activation.

scholarly journals Enhancement of Lipolysis in 3T3-L1 Adipocytes by Nitroarene Capsaicinoid Analogs

2021 ◽  
Vol 16 (1) ◽  
pp. 1934578X2098794
Author(s):  
Thanet Laolob ◽  
Nuntavan Bunyapraphatsara ◽  
Neti Waranuch ◽  
Sutatip Pongcharoen ◽  
Wikorn Punyain ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Calcium Influx ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Binding Interactions ◽  
Π Stacking ◽  
Trpv1 Receptors ◽  
Charge Interaction ◽  
Triglyceride Content ◽  
Transient Receptor

Transient receptor potential vanilloid 1 (TRPV1) activation by capsaicin binding increased intracellular calcium influx and stimulated adipocyte-to-adipocyte communication, leading to lipolysis. Generally, enhancement of π-stacking capabilities improves certain binding interactions. Notably, nitroarenes exhibit strong binding interactions with aromatic amino acid side chains in proteins. New capsaicinoid analogs were designed by substitution of the OCH3 group with a nitrogen dioxide (NO2) group on the vanillyl ring to investigate how π-stacking interactions in capsaicinoid analogs contribute to lipolysis. Capsaicinoid analogs, nitro capsaicin (5), and nitro dihydrocapsaicin (6) were prepared in moderate yields via coupling of a nitroaromatic amine salt and fatty acids. Oil Red O staining and triglyceride assays with 10 µM loading of capsaicin (CAP), dihydrocapsaicin (DHC), 5, and 6 were performed to investigate their effect on lipolysis in 3T3-L1 adipocytes. Both assay results indicated that 5 and 6 decreased lipid accumulation by 13.6% and 14.7%, respectively, and significantly reduced triglyceride content by 26.9% and 28.4%, respectively, in comparison with the control experiment. Furthermore, the decrease in triglyceride content observed in response to nitroarene capsaicinoid analogs was approximately 2-folds higher than that of CAP and DHC. These results arose from the NO2 group augmented π-π stacking with Tyr511 and the attractive charge interaction with Glu570 affecting binding interactions with TRPV1 receptors.

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