scholarly journals TRPM5 is critical for linoleic acid-induced CCK secretion from the enteroendocrine cell line, STC-1

2012 ◽  
Vol 302 (1) ◽  
pp. C210-C219 ◽  
Author(s):  
Bhavik P. Shah ◽  
Pin Liu ◽  
Tian Yu ◽  
Dane R. Hansen ◽  
Timothy A. Gilbertson

Fatty acid-induced stimulation of enteroendocrine cells leads to release of the hormones such as cholecystokinin (CCK) that contribute to satiety. Recently, the fatty acid activated G protein-coupled receptor GPR120 has been shown to mediate long-chain unsaturated free fatty acid-induced CCK release from the enteroendocrine cell line, STC-1, yet the downstream signaling pathway remains unclear. Here we show that linoleic acid (LA) elicits membrane depolarization and an intracellular calcium rise in STC-1 cells and that these responses are significantly reduced when activity of G proteins or phospholipase C is blocked. LA leads to activation of monovalent cation-specific transient receptor potential channel type M5 (TRPM5) in STC-1 cells. LA-induced TRPM5 currents are significantly reduced when expression of TRPM5 or GPR120 is reduced using RNA interference. Furthermore, the LA-induced rise in intracellular calcium and CCK secretion is greatly diminished when expression of TRPM5 channels is reduced using RNA interference, consistent with a role of TRPM5 in LA-induced CCK secretion in STC-1 cells.

2016 ◽  
Vol 28 (2) ◽  
pp. 223
Author(s):  
B. W. Daigneault ◽  
D. J. Miller

Transient receptor potential channel-2 (TRPP2) is a membrane protein important for the regulation of calcium homeostasis in renal epithelial cells. Mutations in human TRPP2 cause enlarged cystic kidneys and contribute to polycystic kidney disease. In addition, TRPP2 functions have been described in some invertebrate sperm and are related to sperm-egg interactions and mating. Male Drosophila with mutated TRPP2 display a mild sperm motility phenotype but have a drastic reduction in fertility due to failed sperm migration and storage within the female tract. Although TRPP2 has critical roles for Drosophila sperm function, the protein has not been described in mammalian sperm. The TRPP2 mutations affecting sperm function could explain idiopathic subfertility that is not detected when evaluating sperm by routine analyses. Herein we report the location of TRPP2 in porcine sperm and have identified functions of TRPP2 in regulating sperm functions important for fertility. The TRPP2 was detected as a 110-kDa band in protein lysates from sperm after capacitation or mock incubation in conditions that do not capacitate sperm. With immunofluorescence, TRPP2 was most abundant on the head and principal piece of sperm with more consistent staining patterns when sperm were maintained in non-capacitating medium. Inhibition of TRPP2 by antiserum resulted in a reduction in sperm average path and curvilinear velocity and an increase in tail cross-beat frequency when sperm were incubated in capacitating conditions. Sperm incubated with TRPP2 antiserum also had a significant decrease in intracellular calcium concentration compared with control samples and failed to undergo an increase in calcium over 90 min that is characteristic of capacitating sperm. TRPP2 is a previously unreported mammalian sperm membrane protein that appears to function as an ion channel to regulate calcium and capacitation-like changes in porcine sperm. This project is supported by Agriculture and Food Research Initiative Competitive Grant no. 2011–67015–20099 and 2015–67015–23228 from the USDA National Institute of Food and Agriculture.


2013 ◽  
Vol 52 (3) ◽  
pp. 425-433 ◽  
Author(s):  
K. Lakshmi Narayanan ◽  
Srinivasa Subramaniam ◽  
C. Peter Bengston ◽  
Krithi Irmady ◽  
Klaus Unsicker ◽  
...  

2003 ◽  
Vol 371 (2) ◽  
pp. 341-350 ◽  
Author(s):  
Helen TURNER ◽  
Andrea FLEIG ◽  
Alexander STOKES ◽  
Jean-Pierre KINET ◽  
Reinhold PENNER

The store-operated calcium-release-activated calcium current, ICRAC, is a major mechanism for calcium entry into non-excitable cells. ICRAC refills calcium stores and permits sustained calcium signalling. The relationship between inositol 1,4,5-trisphosphate receptor (InsP3R)-containing stores and ICRAC is not understood. A model of global InsP3R store depletion coupling with ICRAC activation may be simplistic, since intracellular stores are heterogeneous in their release and refilling activities. Here we use a ligand-gated calcium channel, TRPV1 (transient receptor potential channel, vanilloid subfamily member 1), as a new tool to probe store heterogeneity and define intracellular calcium compartments in a mast cell line. TRPV1 has activity as an intracellular release channel but does not mediate global calcium store depletion and does not invade a store coupled with ICRAC. Intracellular TRPV1 localizes to a subset of the InsP3R-containing stores. TRPV1 sensitivity functionally subdivides the InsP3-sensitive store, as does heterogeneity in the sarcoplasmic/endoplasmic-reticulum Ca2+-ATPase isoforms responsible for store refilling. These results provide unequivocal evidence that a specific ‘CRAC store’ exists within the InsP3-releasable calcium stores and describe a novel methodology for manipulation of intracellular free calcium.


Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 147
Author(s):  
Yu Fu ◽  
Peng Shang ◽  
Bo Zhang ◽  
Xiaolong Tian ◽  
Ruixue Nie ◽  
...  

In animals, muscle growth is a quantitative trait controlled by multiple genes. Previously, we showed that the transient receptor potential channel 1 (TRPC1) gene was differentially expressed in muscle tissues between pig breeds with divergent growth traits base on RNA-seq. Here, we characterized TRPC1 expression profiles in different tissues and pig breeds and showed that TRPC1 was highly expressed in the muscle. We found two single nucleotide polymorphisms (SNPs) (C-1763T and C-1604T) in TRPC1 that could affect the promoter region activity and regulate pig growth rate. Functionally, we used RNAi and overexpression to illustrate that TRPC1 promotes myoblast proliferation, migration, differentiation, fusion, and muscle hypertrophy while inhibiting muscle degradation. These processes may be mediated by the activation of Wnt signaling pathways. Altogether, our results revealed that TRPC1 might promote muscle growth and development and plays a key role in Wnt-mediated myogenesis.


Biomolecules ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 229
Author(s):  
Anna Borgström ◽  
Christine Peinelt ◽  
Paulina Stokłosa

Transient receptor potential melastatin 4 (TRPM4) is widely expressed in various organs and associated with cardiovascular and immune diseases. Lately, the interest in studies on TRPM4 in cancer has increased. Thus far, TRPM4 has been investigated in diffuse large B-cell lymphoma, prostate, colorectal, liver, breast, urinary bladder, cervical, and endometrial cancer. In several types of cancer TRPM4 is overexpressed and contributes to cancer hallmark functions such as increased proliferation and migration and cell cycle shift. Hence, TRPM4 is a potential prognostic cancer marker and a promising anticancer drug target candidate. Currently, the underlying mechanism by which TRPM4 contributes to cancer hallmark functions is under investigation. TRPM4 is a Ca2+-activated monovalent cation channel, and its ion conductivity can decrease intracellular Ca2+ signaling. Furthermore, TRPM4 can interact with different partner proteins. However, the lack of potent and specific TRPM4 inhibitors has delayed the investigations of TRPM4. In this review, we summarize the potential mechanisms of action and discuss new small molecule TRPM4 inhibitors, as well as the TRPM4 antibody, M4P. Additionally, we provide an overview of TRPM4 in human cancer and discuss TRPM4 as a diagnostic marker and anticancer drug target.


2017 ◽  
Vol 204 (5-6) ◽  
pp. 293-303 ◽  
Author(s):  
Masatoshi Fujita ◽  
Tadasu Sato ◽  
Takehiro Yajima ◽  
Eiji Masaki ◽  
Hiroyuki Ichikawa

TRPC (transient receptor potential cation channel subfamily C) members are nonselective monovalent cation channels and control Ca2+ inflow. In this study, immunohistochemistry for TRPC1, TRPC3, and TRPC4 was performed on rat oral and craniofacial structures to elucidate their distribution and function in the peripheries. In the trigeminal ganglion (TG), 56.1, 84.1, and 68.3% of sensory neurons were immunoreactive (IR) for TRPC1, TRPC3, and TRPC4, respectively. A double immunofluorescence method revealed that small to medium-sized TG neurons co-expressed TRPCs and calcitonin gene-related peptide. In the superior cervical ganglion, all sympathetic neurons showed TRPC1 and TRPC3 immunoreactivity. Parasympathetic neurons in the submandibular ganglion, tongue, and parotid gland were TRPC1, TRPC3, and TRPC4 IR. Gustatory and olfactory cells were also IR for TRPC1, TRPC3, and/or TRPC4. In the musculature, motor endplates expressed TRPC1 and TRPC4 immunoreactivity. It is likely that TRPCs are associated with sensory, autonomic, and motor functions in oral and craniofacial structures.


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