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

The prion protein knockout mouse: a phenotype under challenge

The key pathogenic event in prion disease involves misfolding and aggregation of the cellular prion protein (PrP). Beyond this fundamental observation, the mechanism by which PrP misfolding in neurons leads to injury and death remains enigmatic. Prion toxicity may come about by perverting the normal function of PrP. If so, understanding the normal function of PrP may help to elucidate the molecular mechansim of prion disease. Ablation of the Prnp gene, which encodes PrP, was instrumental for determining that the continuous production of PrP is essential for replicating prion infectivity. Since the structure of PrP has not provided any hints to its possible function, and there is no obvious phenotype in PrP KO mice, studies of PrP function have often relied on intuition and serendipity. Here, we enumerate the multitude of phenotypes described in PrP deficient mice, many of which manifest themselves only upon physiological challenge. We discuss the pleiotropic phenotypes of PrP deficient mice in relation to the possible normal function of PrP. The critical question remains open: which of these phenotypes are primary effects of PrP deletion and what do they tell us about the function of PrP

De novo mammalian prion synthesis

Prions are responsible for a heterogeneous group of fatal neurodegenerative diseases. They can be sporadic, genetic, or infectious disorders involving post-translational modifications of the cellular prion protein (PrPC). Prions (PrPSc) are characterized by their infectious property and intrinsic ability to convert the physiological PrPC into the pathological form, acting as a template. The “protein-only” hypothesis, postulated by Stanley B. Prusiner, implies the possibility to generate de novo prions in vivo and in vitro. Here we describe major milestones towards proving this hypothesis, taking into account physiological environment/s, biochemical properties and interactors of the PrPC

Projeto "a escola promovendo hábitos alimentares saudáveis": comparação de duas estratégias de educação nutricional no Distrito Federal, Brasil "Promotion of healthy eating habits by schools" study: comparison of two nutrition education strategies in the Federal District of Brazil

OBJETIVO: Analisar e comparar o conhecimento sobre nutrição de professores e alunos do Projeto "a escola promovendo hábitos alimentares saudáveis", submetidos a duas estratégias de educação nutricional em escolas do Distrito Federal. MÉTODOS: O Projeto Escola utilizou duas estratégias de intervenção em educação nutricional: intervenção nutricional (A) ações educativas realizadas na comunidade escolar pela equipe; e intervenção nutricional (B) ações educativas desenvolvidas por professores que frequentaram oficinas de capacitação. O conhecimento das crianças foi avaliado por meio de um instrumento sobre pirâmide dos alimentos e um sobre higiene pessoal; sendo aplicado com os professores um questionário do tipo verdadeiro ou falso. RESULTADOS: Foram avaliadas 4 escolas com intervenção A (180 alunos e 19 professores) e 4 com intervenção B (129 alunos e 16 professores). A média de acertos no instrumento de pirâmide dos alimentos foi de 3,2 e 2,9 (p=0,37), respectivamente pelas crianças que receberam as intervenções nutricionais A e B. Na atividade sobre higiene pessoal, para estes mesmos alunos, observaram-se percentuais de acerto de 61,1% e 73,6% (p=0,10). Os professores que receberam as intervenções nutricionais A e B obtiveram percentuais de acertos semelhantes nos questionários, em torno de 90,0% (p=0,06). CONCLUSÃO: Observou-se que os dois tipos de intervenção de educação nutricional foram igualmente úteis para promover o conhecimento de alunos e professores. Portanto, faz-se necessário incentivar a realização de processos de educação nutricional no ambiente escolar, de acordo com a diretriz da Política Nacional de Alimentação e Nutrição que diz respeito à promoção da saúde.<br>OBJECTIVE: The objective of this study was to analyze and compare the nutrition knowledge of teachers and students who participated in the study "Promotion of healthy eating habits by schools" and were submitted to two different strategies of nutrition education in schools of the Federal District, Brazil. METHODS: The study administered two strategies of nutrition education intervention: nutrition intervention (A) administration of educational activities in the school community by the research team; and nutrition intervention (B) educational activities were administered by teachers who participated in the training workshops..The knowledge of the students was assessed by an instrument based on the food pyramid and another one based on personal hygiene. The teachers were assessed by means of a true-or-false questionnaire. RESULTS: Four schools submitted to nutrition intervention A (180 students and 19 teachers) and four schools submitted to nutrition intervention B (129 students and 16 teachers) were assessed. The average number of correct answers given by the students on the instrument based on the food pyramid was 3.2 for students in intervention A and 2.9 for students in intervention B (p=0.37). On the instrument about personal hygiene for the same students, 61.1% and 73.6%, respectively, answered it correctly (p=0.10). The teachers submitted to interventions A and B answered a similar number of questions correctly, around 90.0% (p=0.06). CONCLUSION: This study showed that two different types of nutrition education intervention were equally useful to promote nutrition knowledge among teachers and students. Therefore, it is necessary to promote nutrition education programs in schools, in accordance with the National Food and Nutrition Policies, which regard health promotion strategies