Synaptic prion protein immuno-reactivity in the rodent cerebellum

Haeberlé, Anne-Marie; Ribaut‐Barassin, Catherine; Bombarde, Guy; Mariani, Jean; Hunsmann, Gerhard; Grassi, Jacques; Bailly, Yannick

doi:10.1002/1097-0029(20000701)50:1<66::aid-jemt10>3.0.co;2-3

Cited by 52 publications

(33 citation statements)

References 76 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…7A). This observation is in accord with several results previously obtained both in vitro and in vivo with different detection techniques (41)(42)(43)(44)(45)(46)(47)(48).…”

Section: Unglycosylated Prp Localization Is Mainly Intracellular Whesupporting

confidence: 93%

Altered Glycosylated PrP Proteins Can Have Different Neuronal Trafficking in Brain but Do Not Acquire Scrapie-like Properties

Cancellotti

Wiseman

Tuzi

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

N-Linked glycans have been shown to have an important role in the cell biology of a variety of cell surface glycoproteins, including PrP protein. It has been suggested that glycosylation of PrP can influence the susceptibility to transmissible spongiform encephalopathy and determine the characteristics of the many different strains observed in this particular type of disease. To understand the role of carbohydrates in influencing the PrP maturation, stability, and cell biology, we have produced and analyzed gene-targeted murine models expressing differentially glycosylated PrP. Transgenic mice carrying the PrP substitution threonine for asparagine 180 (G1) or threonine for asparagine 196 (G2) or both mutations combined (G3), which eliminate the first, second, and both glycosylation sites, respectively, have been generated by double replacement gene targeting. An in vivo analysis of altered PrP has been carried out in transgenic mouse brains, and our data show that the lack of glycans does not influence PrP maturation and stability. The presence of one chain of sugar is sufficient for the trafficking to the cell membrane, whereas the unglycosylated PrP localization is mainly intracellular. However, this altered cellular localization of PrP does not lead to any overt phenotype in the G3 transgenic mice. Most importantly, we found that, in vivo, unglycosylated PrP does not acquire the characteristics of the aberrant pathogenic form (PrP Sc ), as was previously reported using in vitro models.

show abstract

“…7A). This observation is in accord with several results previously obtained both in vitro and in vivo with different detection techniques (41)(42)(43)(44)(45)(46)(47)(48).…”

Section: Unglycosylated Prp Localization Is Mainly Intracellular Whesupporting

confidence: 93%

Altered Glycosylated PrP Proteins Can Have Different Neuronal Trafficking in Brain but Do Not Acquire Scrapie-like Properties

Cancellotti

Wiseman

Tuzi

et al. 2005

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Thus, a fastidious testing of anti-PrP antibodies should be carried out to confirm positive results (Moya et al 2000;Haeberlé et al 2000). To be successful, this task requires time-consuming steps and several attempts are necessary before the results can be confirmed at the end of the procedure (i.e.…”

Section: Methodological Aspectsmentioning

confidence: 99%

“…The former allows high sensitivity but poor localization (Salès et al 1998;Haeberlé et al 2000;Bailly et al 2004), whereas the latter is less sensitive but gives a more precise subcellular localization (Bailly et al 2004). Finally, the embedding of immunostained material in epoxy resins is helpful in maintaining good morphology.…”

Section: Pre-embedding Methodsmentioning

confidence: 99%

Cellular prion protein electron microscopy: attempts/limits and clues to a synaptic trait. Implications in neurodegeneration process

Fournier

2008

Cell Tissue Res

View full text Add to dashboard Cite

Prion diseases are caused by an infectious agent constituted by a rogue protein called prion (PrP Sc) of neuronal origin (PrP c) and are exemplified by Creutzfeldt-Jakob disease in humans and bovine spongiform encephalopathy in cattle. Considerable efforts have been made to understand the cerebral damage caused by these diseases but a clear comprehensive view cannot be achieved without defining the neurophysiological function of PrP c. This lack of information is in part attributable to our ignorance of the precise localization of PrP c in the brain neuronal cell. One relevant option to explore this aspect is to undertake PrP immunohistochemistry at the electron-microscopy level, knowing that this challenge raises major technical constraints. In describing the attempts and restrictions of the various approaches used, we review here the efforts that have been invested in this particular field of prionology. The common result emerging from these contributions is that the synapse could be the site at which PrP c exerts its critical activity. This location suggests, in the perspective of synaptic regulation, that PrP c can be assigned multiple biological functions and supports the novel concept that prion-like changes are involved in long-term memory formation. The synaptic trait of PrP c and PrP Sc suggests that synapse loss is the key event in neuronal death. Interestingly, synaptic alterations are also considered to be predominant in the pathophysiological mechanism in Alzheimer, Parkinson and Huntington diseases. All these brain disorders, characterized by the formation of a specific amyloid protein of synaptic origin, can be classified under the heading of amyloidogenic synaptopathies.

show abstract

“…Both the NSE and the Prnp promoters are widely expressed in the mouse brain at high levels, and expression is found in many similar brain regions. There is one report of PrP C expression in glial cells (69), but other studies report no PrP C expression in astrocytes and a lack of detectable Prnp mRNA in glia (68,70,71). In transgenic mice that express SGH Prnp driven by the glial fibrillary acidic protein promoter (GFAP), prion incubation periods are very long and disease penetrance is incomplete (72).…”

Section: Fig 8 Western Blot Analysis Of Prpmentioning

confidence: 99%

Host Determinants of Prion Strain Diversity Independent of Prion Protein Genotype

Crowell

Hughson

Caughey

et al. 2015

J Virol

View full text Add to dashboard Cite

Phenotypic diversity in prion diseases can be specified by prion strains in which biological traits are propagated through an epigenetic mechanism mediated by distinct PrP Sc conformations. We investigated the role of host-dependent factors on phenotypic diversity of chronic wasting disease (CWD) in different host species that express the same prion protein gene (Prnp). Two CWD strains that have distinct biological, biochemical, and pathological features were identified in transgenic mice that express the Syrian golden hamster (SGH) Prnp. The CKY strain of CWD had a shorter incubation period than the WST strain of CWD, but after transmission to SGH, the incubation period of CKY CWD was ϳ150 days longer than WST CWD. Limited proteinase K digestion revealed strain-specific PrP Sc polypeptide patterns that were maintained in both hosts, but the solubility and conformational stability of PrP Sc differed for the CWD strains in a host-dependent manner. WST CWD produced PrP Sc amyloid plaques in the brain of the SGH that were partially insoluble and stable at a high concentration of protein denaturant. However, in transgenic mice, PrP Sc from WST CWD did not assemble into plaques, was highly soluble, and had low conformational stability. Similar studies using the HY and DY strains of transmissible mink encephalopathy resulted in minor differences in prion biological and PrP Sc properties between transgenic mice and SGH. These findings indicate that host-specific pathways that are independent of Prnp can alter the PrP Sc conformation of certain prion strains, leading to changes in the biophysical properties of PrP Sc , neuropathology, and clinical prion disease. IMPORTANCEPrions are misfolded pathogenic proteins that cause neurodegeneration in humans and animals. Transmissible prion diseases exhibit a spectrum of disease phenotypes and the basis of this diversity is encoded in the structure of the pathogenic prion protein and propagated by an epigenetic mechanism. In the present study, we investigated prion diversity in two hosts species that express the same prion protein gene. While prior reports have demonstrated that prion strain properties are stable upon infection of the same host species and prion protein genotype, our findings indicate that certain prion strains can undergo dramatic changes in biological properties that are not dependent on the prion protein. Therefore, host factors independent of the prion protein can affect prion diversity. Understanding how host pathways can modify prion disease phenotypes may provide clues on how to alter prion formation and lead to treatments for prion, and other, human neurodegenerative diseases of protein misfolding.

show abstract

Synaptic prion protein immuno-reactivity in the rodent cerebellum

Cited by 52 publications

References 76 publications

Altered Glycosylated PrP Proteins Can Have Different Neuronal Trafficking in Brain but Do Not Acquire Scrapie-like Properties

Altered Glycosylated PrP Proteins Can Have Different Neuronal Trafficking in Brain but Do Not Acquire Scrapie-like Properties

Cellular prion protein electron microscopy: attempts/limits and clues to a synaptic trait. Implications in neurodegeneration process

Host Determinants of Prion Strain Diversity Independent of Prion Protein Genotype

Contact Info

Product

Resources

About