Cellular prion protein binds laminin and mediates neuritogenesis

Graner, Edgard; Mercadante, Adriana F.; Zanata, Sı́lvio M.; Forlenza, Orestes Vicente; Cabral, Ana Lucia Beirão; Veiga, Sílvio Sanches; Juliano, María A.; Roesler, Rafaël; Walz, Roger; Minetti, Alejandra; Izquierdo, Iván; Martins, Vilma R.; Brentani, Ricardo R.

doi:10.1016/s0169-328x(99)00334-4

Cited by 294 publications

(287 citation statements)

References 55 publications

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“…A more extensive search that included sequences for which no three-dimensional structures are available gave Ϸ100 hits, which eventually led to the indication of a significant relationship between PrP segment 146-153 and region 351-358 of the human laminin ␣2 chain, which has the sequence EE-CYYDEN. Because the laminin receptor precursor has been repeatedly suggested as a possible protein partner for PrP C (43)(44)(45), this indication of functional relations between the laminin ␣2 chain and part of the helix ␣1 in PrP C might be worth further study.…”

Section: Discussionmentioning

confidence: 98%

Prion protein NMR structures of chickens, turtles, and frogs

Calzolai

Lysek²,

Pérez³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

168

158

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The NMR structures of the recombinant prion proteins from chicken (Gallus gallus; chPrP), the red-eared slider turtle (Trachemys scripta; tPrP), and the African clawed frog (Xenopus laevis; xlPrP) are presented. The amino acid sequences of these prion proteins show Ϸ30% identity with mammalian prion proteins. All three species form the same molecular architecture as mammalian PrP C , with a long, flexibly disordered tail attached to the N-terminal end of a globular domain. The globular domain in chPrP and tPrP contains three ␣-helices, one short 310-helix, and a short antiparallel ␤-sheet. In xlPrP, the globular domain includes three ␣-helices and a somewhat longer ␤-sheet than in the other species. The spatial arrangement of these regular secondary structures coincides closely with that of the globular domain in mammalian prion proteins. Based on the low sequence identity to mammalian PrPs, comparison of chPrP, tPrP, and xlPrP with mammalian PrP C structures is used to identify a set of essential amino acid positions for the preservation of the same PrP C fold in birds, reptiles, amphibians, and mammals. There are additional conserved residues without apparent structural roles, which are of interest for the ongoing search for physiological functions of PrP C in healthy organisms.nonmammalian species ͉ transmissible spongiform encephalopathy T he prion protein (PrP) has attracted a lot of interest because of its relation to transmissible spongiform encephalopathies (TSEs), which are a group of invariably fatal neurological diseases (1). Healthy organisms that do not express a prion protein, such as suitably selected transgenic laboratory animals, cannot develop a TSE (2), and the ''protein-only hypothesis'' further attributes TSE-causing infectivity to an aggregated ''scrapie form'' of PrP (PrP SC ) that has been isolated from brain tissue of diseased organisms (1). Although TSEs have only been documented for mammalian species, PrP has been identified in a wider range of higher organisms, which on an evolutionary scale extends at least down to amphibians (3-9). In apparent contrast to the high sequence conservation among mammalian PrPs, no physiological function has been reliably attributed to the ''cellular form'' of PrP (PrP C ) found in healthy organisms.In view of its critical role in TSEs, the prion protein has also attracted considerable interest by structural biologists. So far, atomic resolution structure determination was focused on recombinant mammalian prion proteins (10-18), which have recently been shown to represent the protein architecture of PrP C (19). As a group, the mammalian PrPs have Ϸ90% sequence identity (4). Here, we present the NMR structures of recombinant PrP from chicken, turtle, and frog (chPrP, tPrP, and xlPrP, respectively), each of which has Ϸ30% sequence identity with mammalian PrP. We then exploit this low homology in searches, based on comparison of the three-dimensional structures, for conserved amino acids with apparent roles in maintaining a common PrP C -fold, and for nonst...

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Section: Discussionmentioning

confidence: 98%

Prion protein NMR structures of chickens, turtles, and frogs

Calzolai

Lysek²,

Pérez³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

168

158

View full text Add to dashboard Cite

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“…Laminin (an extracellular matrix protein) (56), NCAM (a transmembrane adhesion molecule) (31,32), and STI-1 (a co-chaperone) (57) are important partners that assist in this function of PrP C . Interestingly, these ligands have distinct binding sites on the PrP C molecule and interact with PrP C on the cell surface suggesting that a formation of the macromolecular complex may occur on the plasma membrane in PrP C -dependent neuritogenesis.…”

Section: Discussionmentioning

confidence: 99%

Hemin Interactions and Alterations of the Subcellular Localization of Prion Protein

Lee

Raymond

Schoen

et al. 2007

Journal of Biological Chemistry

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Hemin (iron protoporphyrin IX) is a crucial component of many physiological processes acting either as a prosthetic group or as an intracellular messenger. Some unnatural, synthetic porphyrins have potent anti-scrapie activity and can interact with normal prion protein (PrP C ). These observations raised the possibility that hemin, as a natural porphyrin, is a physiological ligand for PrP C . Accordingly, we evaluated PrP C interactions with hemin. When hemin (3-10 M) was added to the medium of cultured cells, clusters of PrP C formed on the cell surface, and the detergent solubility of PrP C decreased. The addition of hemin also induced PrP C internalization and turnover. The ability of hemin to bind directly to PrP C was demonstrated by hemin-agarose affinity chromatography and UV-visible spectroscopy. Multiple hemin molecules bound primarily to the N-terminal third of PrP C , with reduced binding to PrP C lacking residues 34 -94. These hemin-PrP C interactions suggest that PrP C may participate in hemin homeostasis, sensing, and/or uptake and that hemin might affect PrP C functions.

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“…Two in vitro studies demonstrate that PrP c binds to the laminin receptor 67K (Gauczynski et al, 2001) and the adhesion molecule N-CAM (Santuccione et al, 2005;Schmitt-Ulms et al, 2001), both transducing survival signals or promoting neurite outgrowth. In addition, PrP c mediates neuritogenesis in a laminin-mediated manner (Graner et al, 2000), thereby suggesting that the PrP c -laminin interaction is relevant for neuronal development and further plasticity-related mechanisms. Indeed, Prnp is overexpressed by cortical neurons during axon regeneration and sprouting (JADR et al, unpublished data).…”

Section: Prp C Ligands and Intracellular Signalingmentioning

confidence: 99%

“…Intrinsic Prnp expression is developmentally regulated (Miele et al, 2003) and takes place postnatally in neural tissue (Steele et al, 2006), especially during the fate restriction of multipotential cells towards the neural lineage (Mouillet-Richard et al, 1999), stages characterized by neuronal polarization and synapse formation. Conversely, extracellular PrP c may act via specific receptors in neighboring neurons to promote synapse formation and neuronal maturation (Graner et al, 2000;Kanaani et al, 2005).…”

Section: Introductionmentioning

confidence: 99%