Interaction between the cellular prion (PrPC) and the 2P domain K+ channel TREK-1 protein

Azzalin, Alberto; Ferrara, V.; Arias, Agustina; Cerri, Silvia; Avella, Debora; Pisu, Maria Bonaria; Nano, Rosanna; Bernocchi, Graziella; Ferretti, Luca; Comincini, Sergio

doi:10.1016/j.bbrc.2006.05.097

Cited by 17 publications

(10 citation statements)

References 50 publications

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“…Their analysis confirms that PrP C resides in a membrane environment containing proteins specific of lipid rafts and, in particular, a subset of molecules that, like PrP C , use a GPI-anchor [35]. PrP C interacts with GM3 gangliosides present in high amount in lymphocyte and neuronal lipid rafts [36], [37] and with other glycoproteins or glycolipids [38]–[40], which co-localize or are enriched with PrP C in rafts of neuronal cells. Whether these partners participate in PrP C function is however unknown.…”

Section: Discussionmentioning

confidence: 66%

The Cellular Prion Protein Interacts with the Tissue Non-Specific Alkaline Phosphatase in Membrane Microdomains of Bioaminergic Neuronal Cells

et al. 2009

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BackgroundThe cellular prion protein, PrPC, is GPI anchored and abundant in lipid rafts. The absolute requirement of PrPC in neurodegeneration associated to prion diseases is well established. However, the function of this ubiquitous protein is still puzzling. Our previous work using the 1C11 neuronal model, provided evidence that PrPC acts as a cell surface receptor. Besides a ubiquitous signaling function of PrPC, we have described a neuronal specificity pointing to a role of PrPC in neuronal homeostasis. 1C11 cells, upon appropriate induction, engage into neuronal differentiation programs, giving rise either to serotonergic (1C115-HT) or noradrenergic (1C11NE) derivatives.Methodology/Principal FindingsThe neuronal specificity of PrPC signaling prompted us to search for PrPC partners in 1C11-derived bioaminergic neuronal cells. We show here by immunoprecipitation an association of PrPC with an 80 kDa protein identified by mass spectrometry as the tissue non-specific alkaline phosphatase (TNAP). This interaction occurs in lipid rafts and is restricted to 1C11-derived neuronal progenies. Our data indicate that TNAP is implemented during the differentiation programs of 1C115-HT and 1C11NE cells and is active at their cell surface. Noteworthy, TNAP may contribute to the regulation of serotonin or catecholamine synthesis in 1C115-HT and 1C11NE bioaminergic cells by controlling pyridoxal phosphate levels. Finally, TNAP activity is shown to modulate the phosphorylation status of laminin and thereby its interaction with PrP.Conclusion/SignificanceThe identification of a novel PrPC partner in lipid rafts of neuronal cells favors the idea of a role of PrP in multiple functions. Because PrPC and laminin functionally interact to support neuronal differentiation and memory consolidation, our findings introduce TNAP as a functional protagonist in the PrPC-laminin interplay. The partnership between TNAP and PrPC in neuronal cells may provide new clues as to the neurospecificity of PrPC function.

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Section: Discussionmentioning

confidence: 66%

The Cellular Prion Protein Interacts with the Tissue Non-Specific Alkaline Phosphatase in Membrane Microdomains of Bioaminergic Neuronal Cells

et al. 2009

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“…The interaction was verified in transfected eukaryotic cells by coimmunoprecipitation and by confocal microscopic visualization of the transfected proteins (9). Although the colocalization and binding of PrP C to TREK-1 is interesting, demonstration of the functional consequences of the interaction would highly increase the significance of the finding.…”

Section: Interaction With Partner Proteinsmentioning

confidence: 93%

“…Coexpression of 14-3-3␥ or -decelerated the return of TRESK current to the FIG. 9. Schematic representation of the regulatory protein partners directly interacting with TRESK.…”

Section: B Regulation By Ca 2؉ and Protein Interactionsmentioning

confidence: 99%

Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels

Enyedi

Czirják

2010

Physiological Reviews

760

769

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Two-pore domain K+ (K2P) channels give rise to leak (also called background) K+ currents. The well-known role of background K+ currents is to stabilize the negative resting membrane potential and counterbalance depolarization. However, it has become apparent in the past decade (during the detailed examination of the cloned and corresponding native K2P channel types) that this primary hyperpolarizing action is not performed passively. The K2P channels are regulated by a wide variety of voltage-independent factors. Basic physicochemical parameters (e.g., pH, temperature, membrane stretch) and also several intracellular signaling pathways substantially and specifically modulate the different members of the six K2P channel subfamilies (TWIK, TREK, TASK, TALK, THIK, and TRESK). The deep implication in diverse physiological processes, the circumscribed expression pattern of the different channels, and the interesting pharmacological profile brought the K2P channel family into the spotlight. In this review, we focus on the physiological roles of K2P channels in the most extensively investigated cell types, with special emphasis on the molecular mechanisms of channel regulation.

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“…PrP C also binds to and influences TREK-1 and Ca 2+ -activated ion channels. 96 Thus, PrP C would seem to be directly involved in mechanotransduction, which may be important in mechanotherapy 203 and mechanobiology of the brain, 182 where ion channels can have a significant effect. Mechanical force is also important in membrane dynamics, cytoskeleton and microtubule modulation, and potentially in microtubule-coded communication.…”

Section: Signaling Integrationmentioning

confidence: 99%

“…85 PrP C -null mice, however, are able to grow axons normally, suggesting that there are other mechanisms that can compensate for the loss of PrP C . Nieznanski and coworkers 96,97,181,184 propose that PrP C has a role in α-and β-tubulin oligomerization and competes with microtubule-stabilizing proteins such as stathmin 98 to modulate microtubule stability. The interaction between PrP C and tubulin has also been demonstrated by others, most notably during cell apoptosis, [185][186][187][188] with Schmitz and coworkers finding that PrP C -null mice showed reduced numbers of neurons with β-tubulin in the hippocampus.…”

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confidence: 99%

Prion Protein Signaling in the Nervous System—A Review and Perspective

Liebert

Bicknell

Adams³

2014

Signal Transduction Insights

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Prion protein (PrP C ) was originally known as the causative agent of transmissible spongiform encephalopathy (TSE) but with recent research, its true function in cells is becoming clearer. It is known to act as a scaffolding protein, binding multiple ligands at the cell membrane and to be involved in signal transduction, passing information from the extracellular matrix (ECM) to the cytoplasm. Its role in the coordination of transmitters at the synapse, glyapse, and gap junction and in short-and long-range neurotrophic signaling gives PrP C a major part in neural transmission and nervous system signaling. It acts to regulate cellular function in multiple targets through its role as a controller of redox status and calcium ion flux.

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Interaction between the cellular prion (PrPC) and the 2P domain K+ channel TREK-1 protein

Cited by 17 publications

References 50 publications

The Cellular Prion Protein Interacts with the Tissue Non-Specific Alkaline Phosphatase in Membrane Microdomains of Bioaminergic Neuronal Cells

The Cellular Prion Protein Interacts with the Tissue Non-Specific Alkaline Phosphatase in Membrane Microdomains of Bioaminergic Neuronal Cells

Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels

Prion Protein Signaling in the Nervous System—A Review and Perspective

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Interaction between the cellular prion (PrPC) and the 2P domain K+ channel TREK-1 protein

Cited by 17 publications

References 50 publications

The Cellular Prion Protein Interacts with the Tissue Non-Specific Alkaline Phosphatase in Membrane Microdomains of Bioaminergic Neuronal Cells

The Cellular Prion Protein Interacts with the Tissue Non-Specific Alkaline Phosphatase in Membrane Microdomains of Bioaminergic Neuronal Cells

Molecular Background of Leak K+Currents: Two-Pore Domain Potassium Channels

Prion Protein Signaling in the Nervous System—A Review and Perspective

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Molecular Background of Leak K⁺Currents: Two-Pore Domain Potassium Channels