The TRPM7 channel is inactivated by PIP2 hydrolysis

  title={The TRPM7 channel is inactivated by PIP2 hydrolysis},
  author={Loren W. Runnels and Lixia Yue and David E. Clapham},
  journal={Nature Cell Biology},
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… 

Phosphoinositide regulation of TRP channels.

  • T. Rohacs
  • Biology
    Handbook of experimental pharmacology
  • 2014
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.

Phosphatidylinositol 4,5-Bisphosphate Rescues TRPM4 Channels from Desensitization*

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.

Modulation of TRPs by PIPs

A brief overview of current insights and controversies about the mechanisms and structural determinants of PIP2–TRP channel interactions are provided, and zoom in on the regulation of the Ca2+‐ and voltage‐gated TRPM4 by phosphoinositides.

TRPM7: a unique channel involved in magnesium homeostasis.

Activation of TRPM7 Channels by Phospholipase C-coupled Receptor Agonists*

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.

Phospholipase Cγ1 controls surface expression of TRPC3 through an intermolecular PH domain

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.

Regulation of TRP channels via lipid second messengers.

  • R. Hardie
  • Biology
    Annual review of physiology
  • 2003
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.

The TRP Family of Ion Channels

This review will discuss different mechanisms for Ca2+‐dependent desensitization in TRP channels and propose that the phospholipase C and calmodulin pathways are structurally and functionally coupled.



TRP-PLIK, a Bifunctional Protein with Kinase and Ion Channel Activities

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.

Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol

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.

Direct activation of inward rectifier potassium channels by PIP2 and its stabilization by Gβγ

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.

Activation of the atrial KACh channel by the βγ subunits of G proteins or intracellular Na+ ions depends on the presence of phosphatidylinositol phosphates

It is reported that phosphatidylinositol 4,5-bisphosphate (PIP2) mimics the ATP effects and that depletion or block of PIP2 retards the stimulatory effects of Gβγ subunits or Na+ ions on channel activity, effects that can be reversed by restoring PIP1.

Phospholipase C-linked receptors regulate the ATP-sensitive potassium channel by means of phosphatidylinositol 4,5-bisphosphate metabolism.

  • L. XieM. HorieM. Takano
  • Biology
    Proceedings of the National Academy of Sciences of the United States of America
  • 1999
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 the

The Complex and Intriguing Lives of PIP2 with Ion Channels and Transporters

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.

The trp ion channel family

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.

Polyunsaturated fatty acids activate the Drosophila light-sensitive channels TRP and TRPL

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.

Physiology, Phylogeny, and Functions of the TRP Superfamily of Cation Channels

Investigations into the functions and modes of activation of TRP-related proteins have relevance for human health, because mutations in at least two members of the TRP superfamily are responsible for human diseases.