Prion protein-related proteins from zebrafish are complex glycosylated and contain a glycosylphosphatidylinositol anchor

Miesbauer, Margit; Bamme, Theresa; Riemer, Constanze; Oidtmann, Birgit; Winklhofer, Konstanze F.; Baier, Michael; Tatzelt, Jörg

doi:10.1016/j.bbrc.2005.12.168

Cited by 32 publications

(24 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…En otros trabajos los siRNAs han sido dirigidos contra otras is in agreement with previous reports where the presence of a mRNA for PrP C in the Japanese fugu fish (Takifugu rubripes) was detected (17) . Additionally, in support of the findings on the current study, it has been suggested that fish protein contains a 3D structure similar to PrP C of mammals, and it is also glycosylated and anchored to a glycosylphosphatidylinositol (GPI) molecule (18) . The PrP C of Tilapia was recognized by the mAb 6H4.…”

Section: Discussionsupporting

confidence: 88%

“…), considerando que su presencia puede ser un indicativo de la posibilidad de la adquisición de la enfermedad, encontrando la expresión de PrP C en dichas células, lo que correlaciona con reportes previos donde se detectó la presencia de un mRNA para PrP C en el pez fugu japonés (Takifugu rubripes) (17) . Además, en apoyo a nuestro hallazgo, se ha sugerido que la proteína de peces posee una estructura 3D similar a la PrP C de mamíferos, se encuentra glicosilada y posee glicofosfadil inositol (GPI) como molécula de anclaje (18) . La PrP C de Tilapia fue reconocida mediante el mAb 6H4.…”

Section: Prp C Silencing By Sirnaunclassified

See 1 more Smart Citation

El silenciamiento de la proteína priónica celular (PrPC) mediante RNA de interferencia (siRNA) reduce la infección por HSV-1 y HSV-2 en células SK-SY5Y

Ortega-Soto¹,

Arellano-Anaya²,

Castañeda-Colín³

et al. 2018

Rev. Mex. Cienc. Pecu.

View full text Add to dashboard Cite

RESUMENLas encefalopatías espongiformes transmisibles (EETs) son enfermedades neurodegenerativas fatales que afectan a humanos y ciertas especies animales. La hipótesis más aceptada indica que el agente infeccioso, denotado como prion y compuesto principalmente por la Proteína Priónica Scrapie (PrP Sc ), corresponde a una conformación anormal de una proteína codificada por el huésped denominada Proteína Priónica Celular (PrP C ), cuya función es aún desconocida; sin embargo, la expresión ubicua de PrP C así como su elevado grado de conservación entre especies, sugieren un papel importante para esta proteína. En este trabajo se detectó a la PrP C en diferentes tipos celulares incluyendo un cultivo primario de células de peces (Tilapia, Oreochromis spp.). Además, basándonos en la secuencia de la PrP C humana, se diseñó un RNA de interferencia (siRNA) con el fin de silenciar el gen PRNP en células neuronales SK-SY5Y. El siRNA diseñado inhibió la expresión de PrP C a lo largo de las 96 h post-transfección y las células silenciadas fueron menos susceptibles a la infección por HSV-1 y HSV-2, en comparación con células no transfectadas con el siRNA. PALABRAS CLAVE: Proteína Priónica, PrP C , siRNA, HSV-1, HSV-2. ABSTRACTThe transmissible spongiform encephalopathies (TSEs) are neurodegenerative and fatal diseases, affecting humans and some other animal species. The most accepted hypothesis suggests that the infectious agent, named "prion", is composed mainly by the prion protein scrapie (PrP Sc ) and it corresponds to an abnormal conformation of a host encoded protein, the cellular prion protein (PrP C ), which function is still unknown. However, the ubiquitous expression of PrP C and its highly conserved presence among different species suggests it has a very important role in cell functions. In this work, the PrP C in different cell types, including a primary fish cell culture (Oreochromis spp.), was detected. In addition, based on the human PrP C sequence, we designed a short interfering RNA (siRNA) to silence the PRNP gen in neuronal SK-SY5Y cells. The designed siRNA inhibited the PrP C expression along 96 hours posttransfection and the silenced cells were less susceptible to HSV-1 and HSV-2 infections, in comparison to non siRNA-transfected cells.

show abstract

Section: Discussionsupporting

confidence: 88%

Section: Prp C Silencing By Sirnaunclassified

El silenciamiento de la proteína priónica celular (PrPC) mediante RNA de interferencia (siRNA) reduce la infección por HSV-1 y HSV-2 en células SK-SY5Y

Ortega-Soto¹,

Arellano-Anaya²,

Castañeda-Colín³

et al. 2018

Rev. Mex. Cienc. Pecu.

View full text Add to dashboard Cite

show abstract

“…Anchor-In a previous study, we have shown that zebrafish Sho expressed in mammalian cells is a complex glycosylated, GPIanchored protein present at the outer leaflet of the plasma membrane (23). For a functional characterization of mammalian Sho, we cloned the human homolog and several mutants as outlined in Fig.…”

Section: Sho Mutants Devoid Of the N-terminal Domain Or The Internal mentioning

confidence: 99%

“…The sequence homology between Sho and PrP is restricted to the internal hydrophobic domain; however, certain features, such as a N-terminal repeat region and a C-terminal GPI anchor, are conserved, suggesting that Sho and PrP may be functionally related. Experimental evidence for the post-translational modifications and cell surface localization of Sho was first presented for zebrafish Sho (23) and afterward also for mouse Sho (24). Moreover, it was demonstrated that Sho, similarly to PrP C , can prevent neuronal cell death induced by the expression of PrP⌬HD mutants (24).…”

mentioning

confidence: 99%

Conserved Stress-protective Activity between Prion Protein and Shadoo

Sakthivelu

Seidel

Winklhofer

et al. 2011

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Shadoo (Sho) is a neuronally expressed glycoprotein of unknown function. Although there is no overall sequence homology to the cellular prion protein (PrP C ), both proteins contain a highly conserved internal hydrophobic domain (HD) and are tethered to the outer leaflet of the plasma membrane via a C-terminal glycosylphosphatidylinositol anchor. A previous study revealed that Sho can reduce toxicity of a PrP mutant devoid of the HD (PrP⌬HD). We have now studied the stress-protective activity of Sho in detail and identified domains involved in this activity. Like PrP C , Sho protects cells against physiological stressors such as the excitotoxin glutamate. Moreover, both PrP C and Sho required the N-terminal domain for this activity; the stress-protective capacity of PrP⌬N as well as Sho⌬N was significantly impaired. In both proteins, the HD promoted homodimer formation; however, deletion of the HD had different effects. Although Sho⌬HD lost its stress-protective activity, PrP⌬HD acquired a neurotoxic potential. Finally, we could show that the N-terminal domain of PrP C could be functionally replaced by that of Sho, suggesting a similar function of the N termini of Sho and PrP C . Our study reveals a conserved physiological activity between PrP C and Sho to protect cells from stress-induced toxicity and suggests that Sho and PrP C might act on similar signaling pathways.

show abstract

“…Structurally there are two features which exists in both Shadoo and the PrP's natively unstructured N-terminus: i) a series of positively charged tandem repeats with short sequences ii) a hydrophobic domain (HD) (Figure 2). Also, like the other two members, Sho carries a GPI anchor signal sequences and one or two N-glycosylation sites which were experimentally confirmed on the endogenous protein in brain homogenates (Miesbauer et al, 2006;. Besides these structural similarities, several other correlations have been identified.…”

Section: Figure 2: Schematic Representation Of the Domain Architecturmentioning

confidence: 77%

Investigation of the role of prion protein in protection against transition metal induced toxicity

Cingaram¹

View full text Add to dashboard Cite

Prion protein-related proteins from zebrafish are complex glycosylated and contain a glycosylphosphatidylinositol anchor

Cited by 32 publications

References 18 publications

El silenciamiento de la proteína priónica celular (PrPC) mediante RNA de interferencia (siRNA) reduce la infección por HSV-1 y HSV-2 en células SK-SY5Y

El silenciamiento de la proteína priónica celular (PrPC) mediante RNA de interferencia (siRNA) reduce la infección por HSV-1 y HSV-2 en células SK-SY5Y

Conserved Stress-protective Activity between Prion Protein and Shadoo

Investigation of the role of prion protein in protection against transition metal induced toxicity

Contact Info

Product

Resources

About