Modulation of Serotonergic Receptor Signaling and Cross-talk by Prion Protein*

Mouillet-Richard, Sophie; Pietri, Mathéa; Schneider, Benoı̂t; Vidal, Catherine; Mutel, Vincent; Launay, Jean‐Marie; Kellermann, Odile

doi:10.1074/jbc.m406199200

Cited by 52 publications

(55 citation statements)

References 34 publications

(46 reference statements)

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“…Therefore, the specific contribution of 5HT5A to serotonin-induced accumulation of cAMP in the cerebral cortex is difficult to assert. In this respect, it is particularly relevant to our results that the prion protein was also shown to modulate the activity of at least 3 other serotonin receptors, namely 5HT2B, 5HT1B/D, and 5HT2A, in an inducible serotonergic cell line (23,24).…”

Section: Discussionmentioning

confidence: 73%

“…In particular, antibody-mediated engagement of PrP C reduced signaling through adenylyl cyclase, phospholipases C and A 2 , from at least three subtypes of the G proteincoupled serotonin (5HT) receptor and modulated the crosstalk among these pathways in a cell line that expresses 5HT receptors as well as PrP C (23,24). Monoaminergic systems are disturbed as diseases progress in animal models of transmissible spongiform encephalopathies.…”

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confidence: 99%

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Prion Protein Modulates Monoaminergic Systems and Depressive-like Behavior in Mice

Beckman

Santos

Americo

et al. 2015

Journal of Biological Chemistry

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Background:The prion protein (PrP C ) functions as a scaffold for cell surface signaling systems, and plays a role in neurodegenerative diseases that include clinical depression among their symptoms. Results: PrP C -null mice showed depressive-like behavior concomitant with functional changes in monoaminergic systems. Conclusion: PrP C regulates functions of monoaminergic synapses. Significance: PrP C may be involved in major depression and related neuropsychiatric disorders.

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Section: Discussionmentioning

confidence: 73%

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confidence: 99%

Prion Protein Modulates Monoaminergic Systems and Depressive-like Behavior in Mice

Beckman

Santos

Americo

et al. 2015

Journal of Biological Chemistry

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“…In addition, ␣-secretase regulates the cleavage of PrP C , generating an N-terminal fragment with neuroprotective activity (11,12). PrP C also binds to transmembrane proteins such as the 67-kDa laminin receptor (13)(14)(15), neuronal cell adhesion molecule (16,17), G protein-coupled serotonergic receptors (18), and low density lipoprotein receptor-related protein 1 (19,20), which are able to promote intracellular signaling-mediated neuronal adhesion and differentiation as well as PrP C internalization. Remarkably, PrP C functions as a receptor or co-receptor for extracellular matrix proteins such as laminin (21,22) and vitronectin (23), as well as the secreted co-chaperone stressinducible protein 1 (STI1) (24).…”

Section: -3)mentioning

confidence: 99%

“…Previously, PrP C has been shown to interact with neuronal cell adhesion molecule to stimulate Fyn-kinase (17). Furthermore, PrP C has also been shown to associate with G protein-coupled serotonergic receptors, interfering with the intensities and/or dynamics of G protein activation by agonist-bound 5-HT receptors (18,44). PrP C also acts as a receptor for A␤ 1-42 oligomers to inhibit synaptic plasticity in the form of long term potentiation (7).…”

Section: Journal Of Biological Chemistry 36547mentioning

confidence: 99%

Role of α7 Nicotinic Acetylcholine Receptor in Calcium Signaling Induced by Prion Protein Interaction with Stress-inducible Protein 1

Beraldo

Arantes

Santos

et al. 2010

Journal of Biological Chemistry

106

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The prion protein (PrP C ) is a conserved glycosylphosphatidylinositol-anchored cell surface protein expressed by neurons and other cells. Stress-inducible protein 1 (STI1) binds PrP C extracellularly, and this activated signaling complex promotes neuronal differentiation and neuroprotection via the extracellular signal-regulated kinase 1 and 2 (ERK1/2) and cAMP-dependent protein kinase 1 (PKA) pathways. However, the mechanism by which the PrP C -STI1 interaction transduces extracellular signals to the intracellular environment is unknown. We found that in hippocampal neurons, STI1-PrP C engagement induces an increase in intracellular Ca 2؉ levels. This effect was not detected in PrP C -null neurons or wild-type neurons treated with an STI1 mutant unable to bind PrP C . Using a best candidate approach to test for potential channels involved in Ca 2؉ influx evoked by STI1-PrP C , we found that ␣-bungarotoxin, a specific inhibitor for ␣7 nicotinic acetylcholine receptor (␣7nAChR), was able to block PrP C -STI1-mediated signaling, neuroprotection, and neuritogenesis. Importantly, when ␣7nAChR was transfected into HEK 293 cells, it formed a functional complex with PrP C and allowed reconstitution of signaling by PrP C -STI1 interaction. These results indicate that STI1 can interact with the PrP C ⅐␣7nAChR complex to promote signaling and provide a novel potential target for modulation of the effects of prion protein in neurodegenerative diseases.Prions are the infectious components of transmissible spongiform encephalopathies that can self-perpetuate by imprinting an anomalous conformation onto a glycosylphosphatidylinositol-anchored host protein known as the prion protein (PrP C ). 3Conversion of PrP C to the protease-resistant prion is thought to be a major event in prion diseases (1). However, despite the wealth of knowledge on prions, the roles of PrP C on synaptic function and neuronal health are still not completely understood. Studies in yeast, mammalian cells, and mouse models support the hypothesis that PrP C plays a major role in neuroprotection and neuronal differentiation (for review, see Refs. 1-3).In humans, the initial cognitive dysfunction observed in transmissible spongiform encephalopathies is remarkably similar to those observed in Alzheimer disease (AD). Therefore, synaptic failure is likely to play a major role in the cognitive alterations seen in these neurological disorders (4). For instance, in AD, the role for A␤ ligands in synaptic dysfunction has received considerable attention (5, 6). Interestingly, recent work provided evidence that PrP C functions as a receptor for A␤ and that this interaction mediates some of the effects of A␤ oligomers in synaptic plasticity (7) although these results are controversial at the moment (8, 9). Moreover, PrP C seems to regulate the ␤-secretase cleavage of amyloid precursor protein, thereby regulating the production of A␤ (10). In addition, ␣-secretase regulates the cleavage of PrP C , generating an N-terminal fragment with neuroprotective activity (11,12)...

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“…The interaction of PrP C with STI1 not only activates cyclic adenosine monophosphate (cAMP)-dependent protein-kinase A to transduce a sur- 570 T. ONODERA ET AL vival signal but also induces phosphorylation/activation of the mitogen-activated protein kinase to promote neuritogenesis (57). Recently, PrP C has been demonstrated to modulate serotonergic receptor-signaling in the inducible serotonergic 1C115-HT cell line; viz., modulation of 5-hydroxytryptamine (5-HT) receptor coupling to activate Gprotein functions, as well as acting as a protagonist to promote homeostasis of serotonergic neurons (68). In addition, PrP C binds with extracellular matrix protein laminin to promote genesis and maintenance of neurites (28,29).…”

Section: Prp Sc Detectionmentioning

confidence: 99%

Bovine Spongiform Encephalopathy in Japan: History and Recent Studies on Oxidative Stress in Prion Diseases

Onodera

Sakudo

et al. 2006

Microbiology and Immunology

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With respect to BSE and vCJD, compliance with the following three rules should strictly be observed: (i) Identification and destruction of all clinically affected cattle; (ii) destruction of all mammalian proteins used in feeding ruminant livestock; and (iii) destruction of all high-risk tissues for use in human consumption. Plugging "loopholes" of these rules is the essential factor required to accomplish the task more efficiently. Although compliance with the basic rules is an important issue, global evidence has demonstrated that compliance is imperfect. An important Japanese response to the emergence of this disease was the establishment of independent scientific committees to formulate strategies for adopting relevant disease and control countermeasures. These were the Food Safety Commission (FSC) of the Japanese Government Cabinet Office, and the Prion Expert Committee in the FSC to persistently provide independent advice on said strategies. In addition, the Expert Committee on the Impact of Cattle-Testing assessed the risk of human exposure to BSE agents in Japan. The screening test employed for detection of the expected fraction of BSE-infected cattle destined for slaughter yielded 20%, even if all slaughtered cattle were tested by the ELISA and Western blot. Provided that the removal of specific risk-materials was conducted properly, the discrepancy in changing the age limit to over 20 months of age was negligible for testing beef safety. Scrapie in sheep has been documented in the 18th century in the United Kingdom.

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Modulation of Serotonergic Receptor Signaling and Cross-talk by Prion Protein*

Cited by 52 publications

References 34 publications

Prion Protein Modulates Monoaminergic Systems and Depressive-like Behavior in Mice

Prion Protein Modulates Monoaminergic Systems and Depressive-like Behavior in Mice

Role of α7 Nicotinic Acetylcholine Receptor in Calcium Signaling Induced by Prion Protein Interaction with Stress-inducible Protein 1

Bovine Spongiform Encephalopathy in Japan: History and Recent Studies on Oxidative Stress in Prion Diseases

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