Regulation of ion channels by phosphatidylinositol 4,5-bisphosphate

Suh, Byung Chang; Hille, Bertil

doi:10.1016/j.conb.2005.05.005

Cited by 410 publications

(420 citation statements)

References 67 publications

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“…PIP 2 plays a major regulatory role at the plasma membrane as a precursor for several signaling molecules, e.g., diacylglycerol and IP 3 . Moreover, localized membrane changes in PIP 2 itself are likely an important signal because PIP 2 is known to modulate a variety of channels and transporters (26). PIP 2 has been shown to play a role in a variety of cell functions, including ion channel modulation, rearrangement of cytoskeleton, and membrane protein trafficking (26).…”

Section: Discussionmentioning

confidence: 99%

“…1 A and B). It has been shown that PIP 2 (and not its metabolites) serves as a direct modulator of selected ion channels, including TRPM7 (26,35). Consequently, phospholipase C (PLC)-mediated hydrolysis and depletion of PIP 2 have been shown to inhibit cation entry through the TRPM7 channel (35).…”

Section: ␥-Secretase Inhibitors or Modulators Fail To Restore Mic Curmentioning

confidence: 99%

“…Interestingly, the levels of cellular PIP 2 also closely correlate with levels of A␤42. Given the role of PIP 2 in a variety of cellular processes, including ion channel gating and protein/ membrane trafficking (26), PIP 2 imbalance may play a role in multiple cellular changes associated with presenilin FAD.…”

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confidence: 99%

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Presenilin mutations linked to familial Alzheimer's disease cause an imbalance in phosphatidylinositol 4,5-bisphosphate metabolism

Landman

Jeong

Shin

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

125

121

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Phosphatidylinositol 4,5-bisphosphate (PIP2) is an important cellular effector whose functions include the regulation of ion channels and membrane trafficking. Aberrant PIP 2 metabolism has also been implicated in a variety of human disease states, e.g., cancer and diabetes. Here we report that familial Alzheimer's disease (FAD)-associated presenilin mutations cause an imbalance in PIP 2 metabolism. We find that the transient receptor potential melastatin 7 (TRPM7)-associated Mg 2؉ -inhibited cation (MIC) channel underlies ion channel dysfunction in presenilin FAD mutant cells, and the observed channel deficits are restored by the addition of PIP 2, a known regulator of the MIC/TRPM7 channel. Lipid analyses show that PIP 2 turnover is selectively affected in FAD mutant presenilin cells. We also find that modulation of cellular PIP 2 closely correlates with 42-residue amyloid ␤-peptide (A␤42) levels. Our data suggest that PIP 2 imbalance may contribute to Alzheimer's disease pathogenesis by affecting multiple cellular pathways, such as the generation of toxic A␤42 as well as the activity of the MIC/TRPM7 channel, which has been linked to other neurodegenerative conditions. Thus, our study suggests that brain-specific modulation of PIP 2 may offer a therapeutic approach in Alzheimer's disease.␤-amyloid precursor protein ͉ channel ͉ secretase ͉ transient receptor potential melastatin 7 (TRPM7) ͉ capacitative calcium entry

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Section: Discussionmentioning

confidence: 99%

Section: ␥-Secretase Inhibitors or Modulators Fail To Restore Mic Curmentioning

confidence: 99%

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Presenilin mutations linked to familial Alzheimer's disease cause an imbalance in phosphatidylinositol 4,5-bisphosphate metabolism

Landman

Jeong

Shin

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

125

121

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“…Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P 2 or PIP 2 ) is abundant phosphoinositide in the cell membrane and regulates numerous ion channels and transporters (Suh et al, 2005;Zhao et al, 2007b). To study the relationship between gintonin-mediated I ATP potentiation and the role of phosphoinositides, we used wortmannin.…”

Section: Resultsmentioning

confidence: 99%

Gintonin, a Ginseng-Derived Lysophosphatidic Acid Receptor Ligand, Potentiates ATP-Gated P2X1 Receptor Channel Currents

Choi

Kim

et al. 2013

Molecules and Cells

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Ginseng, the root of Panax ginseng C.A. Meyer, is used as a general tonic. Recently, we isolated a novel ginsengderived lysophosphatidic acid (LPA) receptor ligand, gintonin. Gintonin activates G protein-coupled LPA receptors with high affinity in cells endogenously expressing LPA receptors, e.g., Xenopus oocytes. P2X receptors are ligandgated ion channels activated by extracellular ATP, and 7 receptor subtypes (P2X 1 -P2X 7 ) have been identified. Most of the P2X 1 receptors are expressed in the smooth muscles of genitourinary organs involved in reproduction. A main characteristic of the P2X 1 receptor is rapid desensitization after repeated ATP treatment of cells or tissues expressing P2X 1 receptors. In the present study, we examined the effect of gintonin on P2X 1 receptor channel activity. P2X 1 receptors were heterologously expressed in Xenopus oocytes. ATP treatment of oocytes expressing P2X 1 receptors induced large inward currents (I ATP ), but repetitive ATP treatments induced a rapid desensitization of I ATP . Gintonin treatment after P2X 1 receptor desensitization potentiated I ATP in a concentration-dependent manner. We further examined the signaling transduction pathways involved in gintonin-mediated potentiation of I ATP . Gintonin-mediated I ATP potentiation was blocked by Ki16425, an LPA1/3 receptor antagonist, a PKC inhibitor, a PLC inhibitor, and a PI4-Kinase inhibitor but not by a calcium chelator. In addition, mutations of the phosphoinositide binding site of the P2X 1 receptor greatly attenuated the gintonin-mediated I ATP potentiation. These results indicate that G protein-coupled LPA receptor activation by gintonin is coupled to the potentiation of the desensitized P2X 1 receptor through a phosphoinositide-dependent pathway.

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“…The PLCβ enzymes play critical roles in neural functions, and PLCβ1-and PLCβ4-knockout mice develop epilepsy and ataxia, respectively (Kim et al, 1997). The G q/11 -coupled receptor-PLCβ signaling pathways contribute to neuronal functions through multiple second messengers that cause modulation of ion channels (Anwyl, 1999;Hernandez et al, 2008;Hughes et al, 2007;Suh and Hille, 2005), Ca 2+ release from internal stores (Ross et al, 2005), endocannabinoid release (Kano et al, 2009) and activation of enzymes (Amadio et al, 2006;Delmas et al, 2004). Understanding how these signaling pathways are regulated will undoubtedly lead to a better understanding of their roles in brain functions.…”

Section: Introductionmentioning

confidence: 99%

Intracellular calcium level is an important factor influencing ion channel modulations by PLC-coupled metabotropic receptors in hippocampal neurons

et al. 2013

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Regulation of ion channels by phosphatidylinositol 4,5-bisphosphate

Cited by 410 publications

References 67 publications

Presenilin mutations linked to familial Alzheimer's disease cause an imbalance in phosphatidylinositol 4,5-bisphosphate metabolism

Presenilin mutations linked to familial Alzheimer's disease cause an imbalance in phosphatidylinositol 4,5-bisphosphate metabolism

Gintonin, a Ginseng-Derived Lysophosphatidic Acid Receptor Ligand, Potentiates ATP-Gated P2X1 Receptor Channel Currents

Intracellular calcium level is an important factor influencing ion channel modulations by PLC-coupled metabotropic receptors in hippocampal neurons

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