scholarly journals Orai1 and STIM1 in ER/PM junctions: roles in pancreatic cell function and dysfunction

2016 ◽  
Vol 310 (6) ◽  
pp. C414-C422 ◽  
Author(s):  
Aran Son ◽  
Seonghee Park ◽  
Dong Min Shin ◽  
Shmuel Muallem
Keyword(s):  
Intracellular Signaling ◽  
Transient Receptor Potential ◽  
Cell Function ◽  
Receptor Potential ◽  
Pancreatic Cell ◽  
Pancreatic Acini ◽  
Membrane Contact Sites ◽  
Recent Advances ◽  
Membrane Contact ◽  
Transient Receptor

Membrane contact sites (MCS) are critical junctions that form between the endoplasmic reticulum (ER) and membranes of various organelles, including the plasma membrane (PM). Signaling complexes, including mediators of Ca2+signaling, are assembled within MCS, such as the ER/PM junction. This is most evident in polarized epithelial cells, such as pancreatic cells. Core Ca2+signaling proteins cluster at the apical pole, the site of inositol 1,4,5-trisphosphate-mediated Ca2+release and Orai1/transient receptor potential canonical-mediated store-dependent Ca2+entry. Recent advances have characterized the proteins that tether the membranes at MCS and the role of these proteins in modulating physiological and pathological intracellular signaling. This review discusses recent advances in the characterization of Ca2+signaling at ER/PM junctions and the relation of these junctions to physiological and pathological Ca2+signaling in pancreatic acini.

scholarly journals TRPM7, Magnesium, and Signaling

2019 ◽  
Vol 20 (8) ◽  
pp. 1877 ◽  
Author(s):  
Zhi-Guo Zou ◽  
Francisco J. Rios ◽  
Augusto C. Montezano ◽  
Rhian M. Touyz
Keyword(s):  
Growth Factors ◽  
Intracellular Signaling ◽  
Transient Receptor Potential ◽  
Cell Function ◽  
Divalent Cations ◽  
Receptor Potential ◽  
Cellular Functions ◽  
Pathological Conditions ◽  
Transient Receptor Potential Melastatin ◽  
Transient Receptor

The transient receptor potential melastatin-subfamily member 7 (TRPM7) is a ubiquitously expressed chanzyme that possesses an ion channel permeable to the divalent cations Mg2+, Ca2+, and Zn2+, and an α-kinase that phosphorylates downstream substrates. TRPM7 and its homologue TRPM6 have been implicated in a variety of cellular functions and is critically associated with intracellular signaling, including receptor tyrosine kinase (RTK)-mediated pathways. Emerging evidence indicates that growth factors, such as EGF and VEGF, signal through their RTKs, which regulate activity of TRPM6 and TRPM7. TRPM6 is primarily an epithelial-associated channel, while TRPM7 is more ubiquitous. In this review we focus on TRPM7 and its association with growth factors, RTKs, and downstream kinase signaling. We also highlight how interplay between TRPM7, Mg2+ and signaling kinases influences cell function in physiological and pathological conditions, such as cancer and preeclampsia.

scholarly journals Steroids and TRP Channels: A Close Relationship

2020 ◽  
Vol 21 (11) ◽  
pp. 3819
Author(s):  
Karina Angélica Méndez-Reséndiz ◽  
Óscar Enciso-Pablo ◽  
Ricardo González-Ramírez ◽  
Rebeca Juárez-Contreras ◽  
Tamara Rosenbaum ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Cell Function ◽  
Trp Channels ◽  
Protein Complexes ◽  
Transmembrane Protein ◽  
Receptor Potential ◽  
Long Term Effects ◽  
Close Relationship ◽  
Transient Receptor

Transient receptor potential (TRP) channels are remarkable transmembrane protein complexes that are essential for the physiology of the tissues in which they are expressed. They function as non-selective cation channels allowing for the signal transduction of several chemical, physical and thermal stimuli and modifying cell function. These channels play pivotal roles in the nervous and reproductive systems, kidney, pancreas, lung, bone, intestine, among others. TRP channels are finely modulated by different mechanisms: regulation of their function and/or by control of their expression or cellular/subcellular localization. These mechanisms are subject to being affected by several endogenously-produced compounds, some of which are of a lipidic nature such as steroids. Fascinatingly, steroids and TRP channels closely interplay to modulate several physiological events. Certain TRP channels are affected by the typical genomic long-term effects of steroids but others are also targets for non-genomic actions of some steroids that act as direct ligands of these receptors, as will be reviewed here.

scholarly journals Phospho-Mimetic Mutation at Ser602 Inactivates Human TRPA1 Channel

2020 ◽  
Vol 21 (21) ◽  
pp. 7995
Author(s):  
Kristyna Barvikova ◽  
Ivan Barvik ◽  
Viktor Sinica ◽  
Lucie Zimova ◽  
Viktorie Vlachova
Keyword(s):  
Intracellular Signaling ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Conformational Space ◽  
Signaling Cascades ◽  
Post Translational Modifications ◽  
Allosteric Coupling ◽  
Structural Impact ◽  
Transient Receptor

The Transient Receptor Potential Ankyrin 1 (TRPA1) channel is an integrative molecular sensor for detecting environmental irritant compounds, endogenous proalgesic and inflammatory agents, pressure, and temperature. Different post-translational modifications participate in the discrimination of the essential functions of TRPA1 in its physiological environment, but the underlying structural bases are poorly understood. Here, we explored the role of the cytosolic N-terminal residue Ser602 located near a functionally important allosteric coupling domain as a potential target of phosphorylation. The phosphomimetic mutation S602D completely abrogated channel activation, whereas the phosphonull mutations S602G and S602N produced a fully functional channel. Using mutagenesis, electrophysiology, and molecular simulations, we investigated the possible structural impact of a modification (mutation or phosphorylation) of Ser602 and found that this residue represents an important regulatory site through which the intracellular signaling cascades may act to reversibly restrict or “dampen” the conformational space of the TRPA1 channel and promote its transitions to the closed state.

scholarly journals Role of Gangliosides in Peripheral Pain Mechanisms

2020 ◽  
Vol 21 (3) ◽  
pp. 1005 ◽  
Author(s):  
Péter Sántha ◽  
Ildikó Dobos ◽  
Gyöngyi Kis ◽  
Gábor Jancsó
Keyword(s):  
Ion Channels ◽  
Intracellular Signaling ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Membrane Receptors ◽  
Transient Receptor Potential Vanilloid ◽  
Pain Mechanisms ◽  
Novel Approach ◽  
Transient Receptor ◽  
Nociceptive Ion Channels

Gangliosides are abundantly occurring sialylated glycosphingolipids serving diverse functions in the nervous system. Membrane-localized gangliosides are important components of lipid microdomains (rafts) which determine the distribution of and the interaction among specific membrane proteins. Different classes of gangliosides are expressed in nociceptive primary sensory neurons involved in the transmission of nerve impulses evoked by noxious mechanical, thermal, and chemical stimuli. Gangliosides, in particular GM1, have been shown to participate in the regulation of the function of ion channels, such as transient receptor potential vanilloid type 1 (TRPV1), a molecular integrator of noxious stimuli of distinct nature. Gangliosides may influence nociceptive functions through their association with lipid rafts participating in the organization of functional assemblies of specific nociceptive ion channels with neurotrophins, membrane receptors, and intracellular signaling pathways. Genetic and experimentally induced alterations in the expression and/or metabolism of distinct ganglioside species are involved in pathologies associated with nerve injuries, neuropathic, and inflammatory pain in both men and animals. Genetic and/or pharmacological manipulation of neuronal ganglioside expression, metabolism, and action may offer a novel approach to understanding and management of pain.

SARAF modulates TRPC1, but not TRPC6, channel function in a STIM1-independent manner

2016 ◽  
Vol 473 (20) ◽  
pp. 3581-3595 ◽  
Author(s):  
Letizia Albarrán ◽  
José J. López ◽  
Luis J. Gómez ◽  
Ginés M. Salido ◽  
Juan A. Rosado
Keyword(s):  
Transient Receptor Potential ◽  
Cell Function ◽  
Receptor Potential ◽  
Independent Manner ◽  
Channel Function ◽  
Relevant Role ◽  
Trpc6 Channel ◽  
Transient Receptor ◽  
Trpc1 Channel

Canonical transient receptor potential-1 (TRPC1) is an almost ubiquitously expressed channel that plays a relevant role in cell function. As other TRPC members, TRPC1 forms receptor-operated cation channels that exhibit both STIM1-dependent and store-independent behaviour. The STIM1 inhibitor SARAF (for store-operated Ca2+ entry (SOCE)-associated regulatory factor) modulates SOCE by interaction with the STIM1 region responsible for Orai1 activation (SOAR). Furthermore, SARAF modulates Ca2+ entry through the arachidonate-regulated Ca2+ (ARC) channels, consisting of Orai1 and Orai3 heteropentamers and plasma membrane-resident STIM1. While a role for STIM1–Orai1-mediated signals has been demonstrated, the possible role of SARAF in TRPC1 function remains unknown. Here, we provide evidence for the interaction of SARAF with TRPC1, independently of STIM1 both in STIM1-deficient NG115-401L cells and SH-SY5Y cells endogenously expressing STIM1. Silencing of SARAF expression in STIM1-deficient cells demonstrated that SARAF plays a negative regulatory role in TRPC1-mediated Ca2+ entry. The interaction of SARAF with TRPC1 in STIM1-deficient cells, as well as with the TRPC1 pool not associated with STIM1 in STIM1-expressing cells was enhanced by stimulation with the physiological agonist ATP. In contrast with TRPC1, we found that the interaction between SARAF and TRPC6 was constitutive rather than inducible by agonist stimulation. Furthermore, we found that SARAF expression silencing was without effect on Ca2+ entry evoked by agonists in TRPC6 overexpressing cells, as well as in Ca2+ influx evoked by the TRPC6 activator Hyp9. These findings provide evidence for a new regulator of TRPC1 channel function and highlight the relevance of SARAF in intracellular Ca2+ homeostasis.

scholarly journals Modulation of Transient Receptor Potential (TRP) channels by tyrosine phosphorylation

2020 ◽  
Vol 3 (1) ◽  
pp. 77-87
Author(s):  
Alexandra Manolache ◽  
Teodora Stratulat ◽  
Alexandru Babeș
Keyword(s):  
Oxidative Stress ◽  
Nervous System ◽  
Tyrosine Phosphorylation ◽  
Intracellular Signaling ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Diverse Range ◽  
Transient Receptor ◽  
Intracellular Signaling Molecules

Transient Receptor Potential (TRP) channels are a superfamily of polymodal, non-selective receptors, expressed in the nervous system and several other tissues, where they play many physiological or pathological roles. TRP channels are sensitive to a diverse range of stimuli, such as temperature, osmolarity, oxidative stress, external compounds and intracellular signaling molecules. The activity of TRP channels can be modulated by protein phosphorylation, including tyrosine phosphorylation. In this review, we present the studies carried out so far regarding the modulation of TRP channels by tyrosine phosphorylation.

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