TRPC3-interacting triadic proteins in skeletal muscle

2008 ◽  
Vol 411 (2) ◽  
pp. 399-405 ◽  
Author(s):  
Jin Seok Woo ◽  
Do Han Kim ◽  
Paul D. Allen ◽  
Eun Hui Lee
Keyword(s):  
Skeletal Muscle ◽  
Protein Interactions ◽  
Transient Receptor Potential ◽  
Direct Interaction ◽  
Receptor Potential ◽  
Protein S ◽  
Independent Manner ◽  
Release Channel ◽  
Primary Mouse ◽  
Transient Receptor

The expression of TRPC3 (canonical-type transient receptor potential cation channel type 3) is tightly regulated during skeletal muscle cell differentiation, and a functional interaction between TRPC3 and RyR1 [(ryanodine receptor type 1), an SR (sarcoplasmic reticulum) Ca2+-release channel] regulates the gain of SR Ca2+ release during EC (excitation–contraction) coupling. However, it has not been possible to demonstrate direct protein–protein interactions between TRPC3 and RyR1. To identify possible candidate(s) for a linker protein(s) between TRPC3 and RyR1 in skeletal muscle, in the present study we performed MALDI–TOF (matrix-assisted laser-desorption ionization–time-of-flight) MS analysis of a cross-linked triadic protein complex from rabbit skeletal triad vesicles and co-immunoprecipitation assays using primary mouse skeletal myotubes. From these studies, we found that six triadic proteins, that are known to regulate RyR1 function and/or EC coupling [TRPC1, JP2 (junctophilin 2), homer, mitsugumin 29, calreticulin and calmodulin], interacted directly with TRPC3 in a Ca2+-independent manner. However we again found no direct interaction between TRPC3 and RyR1. TRPC1 was identified as a potential physical link between TRPC3 and RyR1, as it interacted with both TRPC3 and RyR1, and JPs showed subtype-specific interactions with both RyR1 and TRPC3 (JP1–RyR1 and JP2–TRPC3). These results support the hypothesis that TRPC3 and RyR1 are functionally engaged via linker proteins in skeletal muscle.

S165F mutation of junctophilin 2 affects Ca2+ signalling in skeletal muscle

2010 ◽  
Vol 427 (1) ◽  
pp. 125-134 ◽  
Author(s):  
Jin Seok Woo ◽  
Ji-Hye Hwang ◽  
Jae-Kyun Ko ◽  
Noah Weisleder ◽  
Do Han Kim ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Dominant Negative ◽  
Skeletal Muscle Function ◽  
Primary Mouse ◽  
Pkc Protein Kinase C ◽  
Skeletal Myotubes ◽  
Transient Receptor ◽  
Canonical Type

JPs (junctophilins) contribute to the formation of junctional membrane complexes in muscle cells by physically linking the t-tubule (transverse-tubule) and SR (sarcoplasmic reticulum) membranes. In humans with HCM (hypertrophic cardiomyopathy), mutations in JP2 are linked to altered Ca2+ signalling in cardiomyocytes; however, the effects of these mutations on skeletal muscle function have not been examined. In the present study, we investigated the role of the dominant-negative JP2-S165F mutation (which is associated with human HCM) in skeletal muscle. Consistent with the hypertrophy observed in human cardiac muscle, overexpression of JP2-S165F in primary mouse skeletal myotubes led to a significant increase in myotube diameter and resting cytosolic Ca2+ concentration. Single myotube Ca2+ imaging experiments showed reductions in both the excitation–contraction coupling gain and RyR (ryanodine receptor) 1-mediated Ca2+ release from the SR. Immunoprecipitation assays revealed defects in the PKC (protein kinase C)-mediated phosphorylation of the JP2-S165F mutant protein at Ser165 and in binding of JP2-S165F to the Ca2+ channel TRPC3 (transient receptor potential cation canonical-type channel 3) on the t-tubule membrane. Therefore both the hypertrophy and altered intracellular Ca2+ signalling in the JP2-S165F-expressing skeletal myotubes can be linked to altered phosphorylation of JP2 and/or altered cross-talk among Ca2+ channels on the t-tubule and SR membranes.

scholarly journals Trafficking of Stretch-Regulated TRPV2 and TRPV4 Channels Inferred Through Interactomics

Biomolecules ◽  
2019 ◽  
Vol 9 (12) ◽  
pp. 791
Author(s):  
Pau Doñate-Macián ◽  
Jennifer Enrich-Bengoa ◽  
Irene R. Dégano ◽  
David G. Quintana ◽  
Alex Perálvarez-Marín
Keyword(s):  
Protein Interactions ◽  
Transient Receptor Potential ◽  
Cell Structure ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Protein Protein Interactions ◽  
Phosphoinositide Signaling ◽  
Transient Receptor ◽  
Cellular Compartments ◽  
Structure And Activity

Transient receptor potential cation channels are emerging as important physiological and therapeutic targets. Within the vanilloid subfamily, transient receptor potential vanilloid 2 (TRPV2) and 4 (TRPV4) are osmo- and mechanosensors becoming critical determinants in cell structure and activity. However, knowledge is scarce regarding how TRPV2 and TRPV4 are trafficked to the plasma membrane or specific organelles to undergo quality controls through processes such as biosynthesis, anterograde/retrograde trafficking, and recycling. This revision lists and reviews a subset of protein–protein interactions from the TRPV2 and TRPV4 interactomes, which is related to trafficking processes such as lipid metabolism, phosphoinositide signaling, vesicle-mediated transport, and synaptic-related exocytosis. Identifying the protein and lipid players involved in trafficking will improve the knowledge on how these stretch-related channels reach specific cellular compartments.

scholarly journals The transient receptor potential, TRP4, cation channel is a novel member of the family of calmodulin binding proteins

2001 ◽  
Vol 355 (3) ◽  
pp. 663-670 ◽  
Author(s):  
Claudia TROST ◽  
Christiane BERGS ◽  
Nina HIMMERKUS ◽  
Veit FLOCKERZI
Keyword(s):  
Amino Acid ◽  
Ion Channels ◽  
Transient Receptor Potential ◽  
Direct Interaction ◽  
Receptor Potential ◽  
Amino Acid Residues ◽  
Glutathione S Transferase ◽  
Calmodulin Binding ◽  
Transient Receptor

The mammalian gene products, transient receptor potential (trp)1 to trp7, are related to the Drosophila TRP and TRP-like ion channels, and are candidate proteins underlying agonist-activated Ca2+-permeable ion channels. Recently, the TRP4 protein has been shown to be part of native store-operated Ca2+-permeable channels. These channels, most likely, are composed of other proteins in addition to TRP4. In the present paper we report the direct interaction of TRP4 and calmodulin (CaM) by: (1) retention of in vitro translated TRP4 and of TRP4 protein solubilized from bovine adrenal cortex by CaM–Sepharose in the presence of Ca2+, and (2) TRP4–glutathione S-transferase pull-down experiments. Two domains of TRP4, amino acid residues 688–759 and 786–848, were identified as being able to interact with CaM. The binding of CaM to both domains occurred only in the presence of Ca2+ concentrations above 10µM, with half maximal binding occurring at 16.6µM (domain 1) and 27.9µM Ca2+ (domain 2). Synthetic peptides, encompassing the two putative CaM binding sites within these domains and covering amino acid residues 694–728 and 829–853, interacted directly with dansyl–CaM with apparent Kd values of 94–189nM. These results indicate that TRP4/Ca2+-CaM are parts of a signalling complex involved in agonist-induced Ca2+ entry.

scholarly journals TRP and the PDZ Protein, Inad, Form the Core Complex Required for Retention of the Signalplex in Drosophila Photoreceptor Cells

2000 ◽  
Vol 150 (6) ◽  
pp. 1411-1422 ◽  
Author(s):  
Hong-Sheng Li ◽  
Craig Montell
Keyword(s):  
Transient Receptor Potential ◽  
Direct Interaction ◽  
Light Response ◽  
Receptor Potential ◽  
Photoreceptor Cells ◽  
Macromolecular Complex ◽  
Pdz Domains ◽  
The Core ◽  
Transient Receptor ◽  
Drosophila Photoreceptor

The light response in Drosophila photoreceptor cells is mediated by a series of proteins that assemble into a macromolecular complex referred to as the signalplex. The central player in the signalplex is inactivation no afterpotential D (INAD), a protein consisting of a tandem array of five PDZ domains. At least seven proteins bind INAD, including the transient receptor potential (TRP) channel, which depends on INAD for localization to the phototransducing organelle, the rhabdomere. However, the determinants required for localization of INAD are not known. In this work, we showed that INAD was required for retention rather than targeting of TRP to the rhabdomeres. In addition, we demonstrated that TRP bound to INAD through the COOH terminus, and this interaction was required for localization of INAD. Other proteins that depend on INAD for localization, phospholipase C and protein kinase C, also mislocalized. However, elimination of any other member of the signalplex had no impact on the spatial distribution of INAD. A direct interaction between TRP and INAD did not appear to have a role in the photoresponse independent of localization of multiple signaling components. Rather, the primary function of the TRP/ INAD complex is to form the core unit required for localization of the signalplex to the rhabdomeres.

Oxtr/TRPV1 expression and acclimation of skeletal muscle to cold-stress in male mice

2021 ◽  
Author(s):  
Elena Conte ◽  
Adele Romano ◽  
Michela De Bellis ◽  
Maria Luisa De Ceglia ◽  
Maria Rosaria Carratù ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Cold Stress ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Male Mice ◽  
Transient Receptor ◽  
Immunohistochemical Studies ◽  
Circulating Levels

We explored the involvement of Oxytocin receptor (Oxtr)/ Transient-receptor-potential-vanilloid-1 (TRPV1) genes and Oxytocin (Oxt) on the adaptation of skeletal muscle to cold stress challenge in mice. Oxtr expression in hypothalamic paraventricular (PVN), supraoptic nuclei (SON), and hippocampus (HIPP) were evaluated by immunohistochemistry in parallel with the measurement of circulating Oxt. The Oxtr and TRPV1 gene expression in Soleus (SOL) and Tibialis Anterior (TA) muscles were investigated by RT-PCR. Histological studies of the cardiac muscle after cold stress were also performed. Male mice (n=15) were divided into controls maintained at room temperature (RT=24°C), exposed to cold stress (CS) at T=4°C for 6 hours (6h), and 5 days (5d). Immunohistochemical studies showed that Oxtr protein expression increased by 2-fold (p=0.01) in PVN and by 1.5-fold (p=0.0001) in HIPP after 6h and 5d CS, but decreased by 2-fold (p=0.026) in SON at 5d. Both Oxtr and TRPV1 gene expression increased after 6h and 5d CS in SOL and TA muscles. Oxtr vs TRPV1 gene expression in SOL and TA muscles evaluated by regression analysis was linearly correlated following CS at 6h and 5d but not at control temperature of 24+1°C, supporting the hypothesis of coupling between these genes. The circulating levels of Oxt are unaffected after 6h CS but decreased by 0.2-fold (p=0.0141) after 5d CS. This is the first report that Oxtr and TRPV1 expression are upregulated in response to cold acclimation in skeletal muscle. The up-regulation of Oxtr in PVN and HIPP balances the decrease of circulating Oxt.

scholarly journals The Contractile Phenotype of Skeletal Muscle in TRPV1 Knockout Mice Is Gender-Specific and Exercise-Dependent

Life ◽  
2020 ◽  
Vol 10 (10) ◽  
pp. 233
Author(s):  
Aude Lafoux ◽  
Sabine Lotteau ◽  
Corinne Huchet ◽  
Sylvie Ducreux
Keyword(s):  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Transient Receptor Potential ◽  
Heat Stroke ◽  
Receptor Potential ◽  
Muscle Physiology ◽  
Transient Receptor Potential Vanilloid ◽  
Noxious Heat ◽  
Contractile Phenotype ◽  
Transient Receptor

The transient receptor potential vanilloid 1 (TRPV1) belongs to the transient receptor potential superfamily of sensory receptors. TRPV1 is a non-selective cation channel permeable to Ca2+ that is capable of detecting noxious heat temperature and acidosis. In skeletal muscles, TRPV1 operates as a reticular Ca2+-leak channel and several TRPV1 mutations have been associated with two muscle disorders: malignant hyperthermia (MH) and exertional heat stroke (EHS). Although TRPV1−/− mice have been available since the 2000s, TRPV1’s role in muscle physiology has not been thoroughly studied. Therefore, the focus of this work was to characterize the contractile phenotype of skeletal muscles of TRPV1-deficient mice at rest and after four weeks of exercise. As MS and EHS have a higher incidence in men than in women, we also investigated sex-related phenotype differences. Our results indicated that, without exercise, TRPV1−/− mice improved in vivo muscle strength with an impairment of skeletal muscle in vitro twitch features, i.e., delayed contraction and relaxation. Additionally, exercise appeared detrimental to TRPV1−/− slow-twitch muscles, especially in female animals.

scholarly journals Eugenol Inhibits Sodium Currents in Dental Afferent Neurons

2006 ◽  
Vol 85 (10) ◽  
pp. 900-904 ◽  
Author(s):  
C.-K. Park ◽  
H.Y. Li ◽  
K.-Y. Yeon ◽  
S.J. Jung ◽  
S.-Y. Choi ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Inhibitory Effect ◽  
Transient Receptor Potential Vanilloid ◽  
Afferent Neurons ◽  
Patch Clamp Technique ◽  
Independent Manner ◽  
Pre Treatment ◽  
Transient Receptor

Although eugenol is widely used in dentistry, little is known about the molecular mechanisms responsible for its anesthetic properties. In addition to calcium channels, recently demonstrated by our group, there could be another molecular target for eugenol. Using a whole-cell patch-clamp technique, we investigated the effect of eugenol on voltage-gated sodium channel currents ( I Na) in rat dental primary afferent neurons identified by retrograde labeling with a fluorescent dye in maxillary molars. Eugenol inhibited action potentials and I Na in both capsaicin-sensitive and capsaicin-insensitive neurons. The pre-treatment with capsazepine, a competitive antagonist of transient receptor potential vanilloid 1 (TRPV1), failed to block the inhibitory effect of eugenol on I Na, suggesting no involvement of TRPV1. Two types of I Na, tetrodotoxin (TTX)-resistant and TTX-sensitive I Na, were inhibited by eugenol. Our results demonstrated that eugenol inhibits I Na in a TRPV1-independent manner. We suggest that I Na inhibition by eugenol contributes to its analgesic effect.

scholarly journals Mice Lacking Homer 1 Exhibit a Skeletal Myopathy Characterized by Abnormal Transient Receptor Potential Channel Activity

2008 ◽  
Vol 28 (8) ◽  
pp. 2637-2647 ◽  
Author(s):  
Jonathan A. Stiber ◽  
Zhu-Shan Zhang ◽  
Jarrett Burch ◽  
Jerry P. Eu ◽  
Sarah Zhang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Scaffolding Protein ◽  
Channel Activity ◽  
Skeletal Muscle Function ◽  
Cross Sectional ◽  
Transient Receptor ◽  
Duchenne's Muscular Dystrophy

ABSTRACT Transient receptor potential (TRP) channels are nonselective cation channels, several of which are expressed in striated muscle. Because the scaffolding protein Homer 1 has been implicated in TRP channel regulation, we hypothesized that Homer proteins play a significant role in skeletal muscle function. Mice lacking Homer 1 exhibited a myopathy characterized by decreased muscle fiber cross-sectional area and decreased skeletal muscle force generation. Homer 1 knockout myotubes displayed increased basal current density and spontaneous cation influx. This spontaneous cation influx in Homer 1 knockout myotubes was blocked by reexpression of Homer 1b, but not Homer 1a, and by gene silencing of TRPC1. Moreover, diminished Homer 1 expression in mouse models of Duchenne's muscular dystrophy suggests that loss of Homer 1 scaffolding of TRP channels may contribute to the increased stretch-activated channel activity observed in mdx myofibers. These findings provide direct evidence that Homer 1 functions as an important scaffold for TRP channels and regulates mechanotransduction in skeletal muscle.

scholarly journals Role of lysophosphatidic acid in ion channel function and disease

2018 ◽  
Vol 120 (3) ◽  
pp. 1198-1211 ◽  
Author(s):  
Ileana Hernández-Araiza ◽  
Sara L. Morales-Lázaro ◽  
Jesús Aldair Canul-Sánchez ◽  
León D. Islas ◽  
Tamara Rosenbaum
Keyword(s):  
Ion Channels ◽  
Ion Channel ◽  
Lysophosphatidic Acid ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Channel Function ◽  
Transient Receptor ◽  
Lipid Protein Interactions

Lysophosphatidic acid (LPA) is a bioactive phospholipid that exhibits a wide array of functions that include regulation of protein synthesis and adequate development of organisms. LPA is present in the membranes of cells and in the serum of several mammals and has also been shown to participate importantly in pathophysiological conditions. For several decades it was known that LPA produces some of its effects in cells through its interaction with specific G protein-coupled receptors, which in turn are responsible for signaling pathways that regulate cellular function. Among the target proteins for LPA receptors are ion channels that modulate diverse aspects of the physiology of cells and organs where they are expressed. However, recent studies have begun to unveil direct effects of LPA on ion channels, highlighting this phospholipid as a direct agonist and adding to the knowledge of the field of lipid-protein interactions. Moreover, the roles of LPA in pathophysiological conditions associated with the function of some ion channels have also begun to be clarified, and molecular mechanisms have been identified. This review focuses on the effects of LPA on ion channel function under normal and pathological conditions and highlights our present knowledge of the mechanisms by which it regulates the function and expression of N- and T-type Ca++ channels; M-type K+ channel and inward rectifier K+ channel subunit 2.1; transient receptor potential (TRP) melastatin 2, TRP vanilloid 1, and TRP ankyrin 1 channels; and TWIK-related K+ channel 1 (TREK-1), TREK-2, TWIK-related spinal cord K+ channel (TRESK), and TWIK-related arachidonic acid-stimulated K+ channel (TRAAK).

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