title: Identification of novel putative-binding proteins for cellular prion protein and a specific interaction with the STIP1 homology and U-Box-containing protein 1.
abstract: Prion diseases involve the conversion of the endogenous cellular prion protein, PrP(C), into a misfolded infectious isoform, PrP(Sc). Several functions have been attributed to PrP(C), and its role has also been investigated in the olfactory system. PrP(C) is expressed in both the olfactory bulb (OB) and olfactory epithelium (OE) and the nasal cavity is an important route of transmission of diseases caused by prions. Moreover, Prnp(-/-) mice showed impaired behavior in olfactory tests. Given the high PrP(C) expression in OE and its putative role in olfaction, we screened a mouse OE cDNA library to identify novel PrP(C)-binding partners. Ten different putative PrP(C) ligands were identified, which were involved in functions such as cellular proliferation and apoptosis, cytoskeleton and vesicle transport, ubiquitination of proteins, stress response, and other physiological processes. In vitro binding assays confirmed the interaction of PrP(C) with STIP1 homology and U-Box containing protein 1 (Stub1) and are reported here for the first time. Stub1 is a co-chaperone with ubiquitin E3-ligase activity, which is associated with neurodegenerative diseases characterized by protein misfolding and aggregation. Physiological and pathological implications of PrP(C)-Stub1 interaction are under investigation. The PrP(C)-binding proteins identified here are not exclusive to the OE, suggesting that these interactions may occur in other tissues and play general biological roles. These data corroborate the proposal that PrP(C) is part of a multiprotein complex that modulates several cellular functions and provide a platform for further studies on the physiological and pathological roles of prion protein.
authors.affiliation: a Department of Basic Pathology ; Universidade Federal do Paraná ; Curitiba, PR , Brazil ;
authors.forename: Ana Paula Lappas
authors.initials: AP
authors.lastname: Gimenez
authors.affiliation: a Department of Basic Pathology ; Universidade Federal do Paraná ; Curitiba, PR , Brazil ;
authors.forename: Larissa Morato Luciani
authors.initials: LM
authors.lastname: Richter
authors.affiliation: a Department of Basic Pathology ; Universidade Federal do Paraná ; Curitiba, PR , Brazil ;
authors.forename: Mariana Campos
authors.initials: MC
authors.lastname: Atherino
authors.affiliation: a Department of Basic Pathology ; Universidade Federal do Paraná ; Curitiba, PR , Brazil ;
authors.forename: Breno Castello Branco
authors.initials: BC
authors.lastname: Beirão
authors.affiliation: a Department of Basic Pathology ; Universidade Federal do Paraná ; Curitiba, PR , Brazil ;
authors.forename: Celso
authors.initials: C
authors.lastname: Fávaro
authors.affiliation: b Department of Structural and Molecular Biology and Genetics ; Universidade Estadual de Ponta Grossa ; Ponta Grossa, PR , Brazil ;
authors.forename: Michele Dietrich Moura
authors.initials: MD
authors.lastname: Costa
authors.affiliation: a Department of Basic Pathology ; Universidade Federal do Paraná ; Curitiba, PR , Brazil ;
authors.forename: Silvio Marques
authors.initials: SM
authors.lastname: Zanata
authors.affiliation: c Department of Biochemistry ; Universidade de São Paulo ; São Paulo, SP , Brazil.
authors.forename: Bettina
authors.initials: B
authors.lastname: Malnic
authors.affiliation: a Department of Basic Pathology ; Universidade Federal do Paraná ; Curitiba, PR , Brazil ;
authors.forename: Adriana Frohlich
authors.initials: AF
authors.lastname: Mercadante
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D011328:Prions / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D002352:Carrier Proteins; D011328:Prions
keywords: CHIP; Stub1; olfactory epithelium; prion; protein interaction; yeast two-hybrid