Shortest known prion protein allele in highly BSE-susceptible lemurs

We describe the shortest prion protein allele known to date. Surprisingly, it is found as a polymorphism exactly in a species (prosimian lemurs) which seems highly susceptible to oral infection with BSE-derived prions. The truncation of the prion protein we found raises several questions. First, is the truncated octarepeat structure we describe, consisting of two octarepeats, still functional in copper binding? A second question is whether this truncation is related to the remarkable oral infectibility of lemurs with BSE-derived prions. And finally, one could argue that this genotype alone might favour development of a prion disease, even in the absence of exogenous infection

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

BACKGROUND: The cellular prion protein, PrP(C), is GPI anchored and abundant in lipid rafts. The absolute requirement of PrP(C) 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 PrP(C) acts as a cell surface receptor. Besides a ubiquitous signaling function of PrP(C), we have described a neuronal specificity pointing to a role of PrP(C) in neuronal homeostasis. 1C11 cells, upon appropriate induction, engage into neuronal differentiation programs, giving rise either to serotonergic (1C11(5-HT)) or noradrenergic (1C11(NE)) derivatives. METHODOLOGY/PRINCIPAL FINDINGS: The neuronal specificity of PrP(C) signaling prompted us to search for PrP(C) partners in 1C11-derived bioaminergic neuronal cells. We show here by immunoprecipitation an association of PrP(C) 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 1C11(5-HT) and 1C11(NE) cells and is active at their cell surface. Noteworthy, TNAP may contribute to the regulation of serotonin or catecholamine synthesis in 1C11(5-HT) and 1C11(NE) 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/SIGNIFICANCE: The identification of a novel PrP(C) partner in lipid rafts of neuronal cells favors the idea of a role of PrP in multiple functions. Because PrP(C) and laminin functionally interact to support neuronal differentiation and memory consolidation, our findings introduce TNAP as a functional protagonist in the PrP(C)-laminin interplay. The partnership between TNAP and PrP(C) in neuronal cells may provide new clues as to the neurospecificity of PrP(C) function

Prävalenz der Gräserpollen assoziierten lokal allergischen Rhinitis (LAR) in Deutschland an einem Kollektiv von 7841 Patienten

Die LAR ist durch eine lokal spezifische IgE Produktion in der Nasenschleimhaut gekennzeichnet und geht mit negativem Serum IgE und Pricktest einher. Lange wurde hierbei die Diagnose einer nicht allergischen Rhinitis (NAR) gestellt. Mittlerweile gibt es gute Belege für die Existenz der LAR. Ziel unserer Studie war es Prävalenz, klinische Charakteristik und Ausprägungsgrad der LAR bei Patienten mit einer intermittierenden Rhinitis während der Gräserpollensaison zu detektieren und diese der Allergischen Rhinitis (AR) gegenüberzustellen. 7841 Patienten mit Symptomen einer AR zwischen Mai und Juli wurden untersucht. Zur Untersuchung gehörten eine standardisierte Anamnese, Fragebögen zur Bestimmung eines Symptomen- u. Medikamentenscores, Pricktest, Serumprobe, Nasenendoskopie, anteriore Rhinomanometrie, und bei bronchialen Symptomen eine Spirometrie.Eine AR auf Gräserpollen mit positiver Anamnese sowie positiver Prick - u./o. Serumtestung wurde bei 6593 Patienten nachgewiesen. Eine Gräserpollen assoziierte LAR konnte bei positiver Anamnese, einem positiven nasalen Provokationstest (NPT) mit einem aus 6 Gräsern und Roggen bestehenden Allergenextrakt u./o. einem positiven spez. IgE Nachweis im Nasensekret (NS), bei gleichzeitig negativer Haut - u. In-vitro Testung, in 38 Fällen diagnostiziert werden. 1210 wurden mittels Prick, Serum-IgE, NPT u. NS IgE Bestimmung auf andere nicht so häufig vorkommende Aeroallergene im o.g. Zeitraum (wie z.B. Ambrosia, Buche, Eiche etc.) getestet. 1008 wiesen eine AR auf die neu getesteten Allergene und 9 eine LAR auf. 123 hatten eine NAR bei negativem Befund und 65 wiesen eine NAR sowie eine unbedeutende Sensibilisierung auf andere Allergene auf. Ob eine AIT im Fall einer LAR Erfolg verspricht, ist derzeit Gegenstand klinischer Studien.Der Erstautor gibt keinen Interessenkonflikt an

Olfactory behavior and physiology are disrupted in prion protein knockout mice

The prion protein PrP(C) is infamous for its role in disease, but its normal physiological function remains unknown. Here we found a previously unknown behavioral phenotype of Prnp(-/-) mice in an odor-guided task. This phenotype was manifest in three Prnp knockout lines on different genetic backgrounds, which provides strong evidence that the phenotype is caused by a lack of PrP(C) rather than by other genetic factors. Prnp(-/-) mice also showed altered behavior in a second olfactory task, suggesting that the phenotype is olfactory specific. Furthermore, PrP(C) deficiency affected oscillatory activity in the deep layers of the main olfactory bulb, as well as dendrodendritic synaptic transmission between olfactory bulb granule and mitral cells. Notably, both the behavioral and electrophysiological alterations found in Prnp(-/-) mice were rescued by transgenic neuronal-specific expression of PrP(C). These data suggest that PrP(C) is important in the normal processing of sensory information by the olfactory system