Regulation of sub-compartmental targeting and folding properties of the Prion-like protein Shadoo

Anna Pepe; Rosario Avolio; D.S. Matassa; Franca Esposito; Lucio Nitsch; Chiara Zurzolo; Simona Paladino; Daniela Sarnataro

Regulation of sub-compartmental targeting and folding properties of the Prion-like protein Shadoo

Anna Pepe ^{1, 2} Rosario Avolio ¹ D.S. Matassa ¹ Franca Esposito ¹ Lucio Nitsch ¹ Chiara Zurzolo ^{2, 1} Simona Paladino ^{3, 1} Daniela Sarnataro ^{1, 3}

1 "Federico II" University of Naples Medical School

2 Trafic membranaire et Pathogénèse

3 CEINGE Biotecnologie Avanzate s.c.a.r.l.

Abstract : Shadoo (Sho), a member of prion protein family, has been shown to prevent embryonic lethality in Prnp 0/0 mice and to be reduced in the brains of rodents with terminal prion diseases. Sho can also affect PrP structural dynamics and can increase the prion conversion into its misfolded isoform (PrPSc), which is amyloidogenic and strictly related to expression, intracellular localization and association of PrPC to lipid rafts. We reasoned that if Sho possesses a natural tendency to convert to amyloid-like forms in vitro, it should be able to exhibit "prion-like" properties, such as PK-resistance and aggregation state, also in live cells. We tested this hypothesis, by different approaches in neuronal cells, finding that Sho shows folding properties partially dependent on lipid rafts integrity whose alteration, as well as proteasomal block, regulated generation of intermediate Sho isoforms and exacerbated its misfolding. Moreover, a 18 kDa isoform of Sho, likely bearing the signal peptide, was targeted to mitochondria by interacting with the molecular chaperone TRAP1 which, in turn controlled Sho dual targeting to ER or mitochondria. Our studies contribute to understand the role of molecular chaperones and of PrP-related folding intermediates in "prion-like" conversion. © 2017 The Author(s).

Keywords : Protein folding Membrane trafficking

Document type :

Journal articles

Domain :

Life Sciences [q-bio]

Complete list of metadatas

Cited literature [56 references] Display Hide Download

https://hal-pasteur.archives-ouvertes.fr/pasteur-01570225
Contributor : Floran Bidault <>
Submitted on : Friday, July 28, 2017 - 4:21:04 PM
Last modification on : Tuesday, October 10, 2017 - 1:41:18 PM

Regulation of sub-compartmental targeting and folding properties of the Prion-like protein Shadoo

File

Licence

Identifiers

Collections

Citation

Export

Metrics

237

57

Contact

Regulation of sub-compartmental targeting and folding properties of the Prion-like protein Shadoo

File

Licence

Identifiers

Collections

Citation

Export

Share

Metrics

237

57

Contact