The TRPM7 channel is inactivated by PIP2 hydrolysis

@article{Runnels2002TheTC,
  title={The TRPM7 channel is inactivated by PIP2 hydrolysis},
  author={Loren W. Runnels and Lixia Yue and David E. Clapham},
  journal={Nature Cell Biology},
  year={2002},
  volume={4},
  pages={329-336}
}
TRPM7 (ChaK1, TRP-PLIK, LTRPC7) is a ubiquitous, calcium-permeant ion channel that is unique in being both an ion channel and a serine/threonine kinase. The kinase domain of TRPM7 directly associates with the C2 domain of phospholipase C (PLC). Here, we show that in native cardiac cells and heterologous expression systems, Gαq-linked receptors or tyrosine kinase receptors that activate PLC potently inhibit channel activity. Numerous experimental approaches demonstrated that phosphatidylinositol… Expand
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PIP2 breakdown appears to be a required step in TRPC4α channel activation as PIP2 depletion alone was insufficient for channel opening, which additionally required Ca2+ and pertussis toxin-sensitive Gi/o proteins. Expand
PIP2 Activates KCNQ Channels, and Its Hydrolysis Underlies Receptor-Mediated Inhibition of M Currents
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This work shows that a common feature of all KCNQ channels is their activation by the signaling membrane phospholipid phosphatidylinositol-bis-phosphate (PIP(2). Expand
Phosphoinositide regulation of TRP channels.
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  • Handbook of experimental pharmacology
  • 2014
TLDR
This chapter will provide a comprehensive overview of the literature on regulation of TRP channels by membrane phosphoinositides with a focus on phosphatidylinositol 4,5 bisphosphate. Expand
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TLDR
The results suggest that PI(4,5)P2 acts to uncouple channel opening from changes in the transmembrane potential, allowing current activation at physiological voltages and argue that hydrolysis of PI( 4,5]P2 underlies desensitization of TRPM4 and support the idea that PI (4, 5)P 2 is a general regulator for the gating of TR PM ion channels. Expand
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TLDR
The biological functions of TRPM7 are discussed, emphasizing its role in development and the potential pathophysiological significance ofTRPM7 in neurological and cardiovascular disease. Expand
Activation of TRPM7 Channels by Phospholipase C-coupled Receptor Agonists*
TLDR
The regulation of TRPM7 by PLC-coupled receptor agonists such as bradykinin, lysophosphatidic acid, and thrombin is examined and it is shown that the TR PM7-dependent Ca2+ increase closely correlates with activation of PLC. Expand
Phospholipase Cγ1 controls surface expression of TRPC3 through an intermolecular PH domain
TLDR
It is reported that the partial PH domain of PLC-γ1 interacts with a complementary partial PH-like domain in TRPC3 to elicit lipid binding and cell-surface expression ofTRPC3. Expand
Regulation of TRP channels via lipid second messengers.
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  • Biology, Medicine
  • Annual review of physiology
  • 2003
TLDR
In Drosophila photoreceptors, diacylglycerol kinase is identified as a key enzyme required for response termination, and mutants of this pathway in combination with genetically targeted PIP2 reporters provide unique insights into the kinetics and regulation of PIP1 turnover. Expand
Integration of phosphoinositide- and calmodulin-mediated regulation of TRPC6.
TLDR
It is proposed that regulation of CaM binding by PIs provides a mode for integration of channel regulation by Ca(2+) and PIs and is applied to other TRP channels, such as TRPV1, as well as to the voltage-gated channels KCNQ1 and Ca(v)1. Expand
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TLDR
Cloned and characterized a protein kinase and ion channel, TRP-PLIK, and inactivation of the kinase activity by site-directed mutagenesis and the channel's dependence on intracellular adenosine triphosphate (ATP) demonstrated that the channel’s Kinase activity is essential for channel function. Expand
Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol
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The molecular mechanism of store-depletion-independent activation of a subfamily of mammalian TRPC channels is described and it is found that hTRPC6 is a non-selective cation channel that is activated by diacylglycerol in a membrane-delimited fashion, independently of protein kinases C activated bydiacyl Glycerol. Expand
Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gβγ
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It is reported that several cloned inward rectifier K+ channels directly bind PIP2, and that this binding correlates with channel activity and coexpression of Gβγ with GIRK channels slows the inhibition of K+ currents by PIP1 antibodies. Expand
Activation of the atrial KACh channel by the βγ subunits of G proteins or intracellular Na+ ions depends on the presence of phosphatidylinositol phosphates
The βγ subunits of GTP-binding proteins (Gβγ) activate the muscarinic K+ channel (KACh) in heart by direct binding to both of its component subunits. KACh channels can also be gated by internal Na+Expand
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In the COS7 cells transfected with cDNAs of the Kir6.2, SUR2A, and M(1) muscarinic receptors, we activated the ATP-sensitive potassium (K(ATP)) channel with a K(+) channel opener and recorded theExpand
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A related biological role of PIP2 may be to control the activity of ion transporters and channels during biosynthesis or vesicle trafficking, which is used by cells to control ion channel and transporter activities. Expand
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Three subgroups comprise the TRP channel family; the best understood of these mediates responses to painful stimuli, and other proposed functions include repletion of intracellular calcium stores, receptor-mediated excitation and modulation of the cell cycle. Expand
Polyunsaturated fatty acids activate the Drosophila light-sensitive channels TRP and TRPL
TLDR
It is suggested that another polyunsaturated fatty acid, such as linolenic acid, may be a messenger of excitation in Drosophila photoreceptors, as four different lipoxygenase inhibitors, which might be expected to lead to build-up of endogenous fatty acids, also activate native TRP and TRPL channels in intact photoresceptors. Expand
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Drosophila phototransduction is a G protein-coupled, calcium-regulated signaling cascade that serves as a model system for the dissection of phospholipase C signaling in vivo and it is demonstrated that TRP and TRPL ion channels can serve partially overlapping functions. Expand
Calcium Influx via TRP Channels Is Required to Maintain PIP2 Levels in Drosophila Photoreceptors
TLDR
The results suggest that Ca2+ influx prevents PIP2 depletion by inhibiting PLC activity and facilitating PIP1 recycling and preventing inactivation in trp. Expand
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