Insights into the physiological function of cellular prion protein
Prions have been extensively studied since they represent a new class of infectious agents in which a protein, PrPsc (prion scrapie), appears to be the sole component of the infectious particle. They are responsible for transmissible spongiform encephalopathies, which affect both humans and animals....
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Associação Brasileira de Divulgação Científica
2001-01-01
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| Series: | Brazilian Journal of Medical and Biological Research |
| Subjects: | |
| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2001000500005 |
| _version_ | 1811314517225766912 |
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| author | Martins V.R. Mercadante A.F. Cabral A.L.B. Freitas A.R.O. Castro R.M.R.P.S. |
| author_facet | Martins V.R. Mercadante A.F. Cabral A.L.B. Freitas A.R.O. Castro R.M.R.P.S. |
| author_sort | Martins V.R. |
| collection | DOAJ |
| description | Prions have been extensively studied since they represent a new class of infectious agents in which a protein, PrPsc (prion scrapie), appears to be the sole component of the infectious particle. They are responsible for transmissible spongiform encephalopathies, which affect both humans and animals. The mechanism of disease propagation is well understood and involves the interaction of PrPsc with its cellular isoform (PrPc) and subsequently abnormal structural conversion of the latter. PrPc is a glycoprotein anchored on the cell surface by a glycosylphosphatidylinositol moiety and expressed in most cell types but mainly in neurons. Prion diseases have been associated with the accumulation of the abnormally folded protein and its neurotoxic effects; however, it is not known if PrPc loss of function is an important component. New efforts are addressing this question and trying to characterize the physiological function of PrPc. At least four different mouse strains in which the PrP gene was ablated were generated and the results regarding their phenotype are controversial. Localization of PrPc on the cell membrane makes it a potential candidate for a ligand uptake, cell adhesion and recognition molecule or a membrane signaling molecule. Recent data have shown a potential role for PrPc in the metabolism of copper and moreover that this metal stimulates PrPc endocytosis. Our group has recently demonstrated that PrPc is a high affinity laminin ligand and that this interaction mediates neuronal cell adhesion and neurite extension and maintenance. Moreover, PrPc-caveolin-1 dependent coupling seems to trigger the tyrosine kinase Fyn activation. These data provide the first evidence for PrPc involvement in signal transduction. |
| first_indexed | 2024-04-13T11:14:07Z |
| format | Article |
| id | doaj.art-2ab56b8c73964c98bf74d7f3deafaf87 |
| institution | Directory Open Access Journal |
| issn | 0100-879X 0034-7310 |
| language | English |
| last_indexed | 2024-04-13T11:14:07Z |
| publishDate | 2001-01-01 |
| publisher | Associação Brasileira de Divulgação Científica |
| record_format | Article |
| series | Brazilian Journal of Medical and Biological Research |
| spelling | doaj.art-2ab56b8c73964c98bf74d7f3deafaf872022-12-22T02:49:02ZengAssociação Brasileira de Divulgação CientíficaBrazilian Journal of Medical and Biological Research0100-879X0034-73102001-01-01345585595Insights into the physiological function of cellular prion proteinMartins V.R.Mercadante A.F.Cabral A.L.B.Freitas A.R.O.Castro R.M.R.P.S.Prions have been extensively studied since they represent a new class of infectious agents in which a protein, PrPsc (prion scrapie), appears to be the sole component of the infectious particle. They are responsible for transmissible spongiform encephalopathies, which affect both humans and animals. The mechanism of disease propagation is well understood and involves the interaction of PrPsc with its cellular isoform (PrPc) and subsequently abnormal structural conversion of the latter. PrPc is a glycoprotein anchored on the cell surface by a glycosylphosphatidylinositol moiety and expressed in most cell types but mainly in neurons. Prion diseases have been associated with the accumulation of the abnormally folded protein and its neurotoxic effects; however, it is not known if PrPc loss of function is an important component. New efforts are addressing this question and trying to characterize the physiological function of PrPc. At least four different mouse strains in which the PrP gene was ablated were generated and the results regarding their phenotype are controversial. Localization of PrPc on the cell membrane makes it a potential candidate for a ligand uptake, cell adhesion and recognition molecule or a membrane signaling molecule. Recent data have shown a potential role for PrPc in the metabolism of copper and moreover that this metal stimulates PrPc endocytosis. Our group has recently demonstrated that PrPc is a high affinity laminin ligand and that this interaction mediates neuronal cell adhesion and neurite extension and maintenance. Moreover, PrPc-caveolin-1 dependent coupling seems to trigger the tyrosine kinase Fyn activation. These data provide the first evidence for PrPc involvement in signal transduction.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2001000500005PrPccellular functiontransmissible spongiform encephalopathieslamininsignal transductioncopper |
| spellingShingle | Martins V.R. Mercadante A.F. Cabral A.L.B. Freitas A.R.O. Castro R.M.R.P.S. Insights into the physiological function of cellular prion protein Brazilian Journal of Medical and Biological Research PrPc cellular function transmissible spongiform encephalopathies laminin signal transduction copper |
| title | Insights into the physiological function of cellular prion protein |
| title_full | Insights into the physiological function of cellular prion protein |
| title_fullStr | Insights into the physiological function of cellular prion protein |
| title_full_unstemmed | Insights into the physiological function of cellular prion protein |
| title_short | Insights into the physiological function of cellular prion protein |
| title_sort | insights into the physiological function of cellular prion protein |
| topic | PrPc cellular function transmissible spongiform encephalopathies laminin signal transduction copper |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2001000500005 |
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