Structural basis of PI(4,5)P2-dependent regulation of GluA1 by phosphatidylinositol-5-phosphate 4-kinase, type II, alpha (PIP5K2A)

Seebohm, Guiscard; Wrobel, Eva; Pusch, Michael; Dicks, Markus; Terhag, Jan; Matschke, Veronika; Rothenberg, Ina; Ursu, Oana; Hertel, Fabian; Pott, Lutz; Läng, Florian; Schulze‐Bahr, Eric; Hollmann, Michael; Stoll, Raphael; Strutz‐Seebohm, Nathalie

doi:10.1007/s00424-013-1424-8

Cited by 16 publications

(25 citation statements)

References 45 publications

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“…While GSK3β is involved in downregulation of AMPARs (Beattie et al, ; Collingridge et al, ; Wei et al, ), several studies indicate the importance of PI3K and AKT in the upregulation of AMPARs (Man et al, ; Qin et al, ). These data are further supported by a very recent finding showing that PIP5K2A, the effector of AKT, may regulate the expression of the GluA1 subunit of AMPARs (Seebohm et al, ). Hence, the interplay between AKT and GSK3β activities may reflect the general mechanism of AMPAR regulation and function, depending on its subunit composition and balance in the post‐synaptic compartment, consequently affecting eLTP expression.…”

Section: Introductionsupporting

confidence: 72%

Membrane-tethered AKT kinase regulates basal synaptic transmission and early phase LTP expression by modulation of post-synaptic AMPA receptor level

et al. 2016

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The serine/threonine kinase AKT/PKB plays a fundamental role in a wide variety of neuronal functions, including neuronal cell development, axonal growth, and synaptic plasticity. Multiple evidence link AKT signaling pathways to regulation of late phase long-term synaptic plasticity, synaptogenesis, and spinogenesis, as well as long-term memory formation. Nevertheless, the downstream effectors mediating the effects of AKT on early phase long-term potentiation (eLTP) are currently unknown. Here we report that using different regimes of pharmacological activation and inhibition of AKT activity in acute hippocampal slices, we found that AKT regulates the post-synaptic expression of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPA) receptors affecting solely the expression of eLTP, with no effect on its induction and maintenance. We further show that both maintenance of basal synaptic activity and expression of eLTP require plasma membrane tethering by activated AKT and that basal synaptic activity may be regulated via the direct effects of AKT1 on the expression level of post-synaptic AMPA receptors bypassing the canonical AKT signaling. Finally, we establish that eLTP expression requires the involvement of both the canonical AKT signaling pathways and the direct effect of AKT1 on AMPA receptor activity/expression in the post-synaptic membrane. © 2016 Wiley Periodicals, Inc.

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Section: Introductionsupporting

confidence: 72%

Membrane-tethered AKT kinase regulates basal synaptic transmission and early phase LTP expression by modulation of post-synaptic AMPA receptor level

et al. 2016

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“…Protein binding to relevant lipids can be detected with antibodies to the tagged protein. This method has been used for example to confirm binding of PIP 2 to the GluA1 ionotropic glutamate receptor (Seebohm et al, 2014). The results from this assay (N = 5 biological repeats; see SI Fig have an elevated level of PI(4)P (Garcia et al, 2018;Nakatsu, 2015).…”

Section: Free Energy Landscapes For Pc2/lipid Interactionsmentioning

confidence: 99%

Lipid Interactions of a Ciliary Membrane TRP Channel: Simulation and Structural Studies of Polycystin-2 (PC2)

Wang

Hedger

Aryal

et al. 2019

Preprint

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Polycystin-2 (PC2) is a member of the TRPP subfamily of TRP channels and is present in ciliary membranes of the kidney. PC2 can be either homo-tetrameric, or heterotetrameric with PC1. PC2 shares a common transmembrane fold with other TRP channels, in addition to having a novel extracellular domain. Several TRP channels have been suggested to be regulated by lipids, including phosphatidylinositol phosphates (PIPs). We have combined molecular dynamics simulations with cryoelectron microscopy to explore possible lipid interactions sites on PC2. We propose that PC2 has a PIP-binding site close to the equivalent vanilloid/lipid-binding site in the TRPV1 channel. A 3.0 Å cryoelectron microscopy map reveals a binding site for cholesterol on PC2. Cholesterol interactions with the channel at this site are further characterized by MD simulations. These results help to position PC2 within an emerging model of the complex roles of lipids in the regulation and organization of ciliary membranes.

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“…Lipid Binding Assay-The assay was recently described in detail (31). In brief, PIP Strips from Molecular Probes were used (P23750).…”

mentioning

confidence: 99%

Novel Kv7.1-Phosphatidylinositol 4,5-Bisphosphate Interaction Sites Uncovered by Charge Neutralization Scanning

Eckey

Wrobel

Strutz‐Seebohm

et al. 2014

Journal of Biological Chemistry

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Structural basis of PI(4,5)P2-dependent regulation of GluA1 by phosphatidylinositol-5-phosphate 4-kinase, type II, alpha (PIP5K2A)

Cited by 16 publications

References 45 publications

Membrane-tethered AKT kinase regulates basal synaptic transmission and early phase LTP expression by modulation of post-synaptic AMPA receptor level

Membrane-tethered AKT kinase regulates basal synaptic transmission and early phase LTP expression by modulation of post-synaptic AMPA receptor level

Lipid Interactions of a Ciliary Membrane TRP Channel: Simulation and Structural Studies of Polycystin-2 (PC2)

Novel Kv7.1-Phosphatidylinositol 4,5-Bisphosphate Interaction Sites Uncovered by Charge Neutralization Scanning

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