Web of Science: 8 cites, Scopus: 8 cites, Google Scholar: cites,
The prion-like RNA-processing protein HNRPDL forms inherently toxic amyloid-like inclusion bodies in bacteria
Navarro Cantero, Susana (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Marinelli, Patrizia (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Díaz-Caballero, Marta (Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Ventura, Salvador (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)

Data: 2015
Resum: Background: rhe formation of protein inclusions is connected to the onset of many human diseases. Human RNA binding proteins containing intrinsically disordered regions with an amino acid composition resembling those of yeast prion domains, like TDP-43 or FUS, are being found to aggregate in different neurodegenerative disorders. The structure of the intracellular inclusions formed by these proteins is still unclear and whether these deposits have an amyloid nature or not is a matter of debate. Recently, the aggregation of TDP-43 has been modelled in bacteria, showing that TDP-43 inclusion bodies (IBs) are amorphous but intrinsically neurotoxic. This observation raises the question of whether it is indeed the lack of an ordered structure in these human prion-like protein aggregates the underlying cause of their toxicity in different pathological states. - Results: here we characterize the IBs formed by the human prion-like RNA-processing protein HNRPDL. HNRPDL is linked to the development of limb-girdle muscular dystrophy 1G and shares domain architecture with TDP-43. We show that HNRPDL IBs display characteristic amyloid hallmarks, since these aggregates bind to amyloid dyes in vitro and inside the cell, they are enriched in intermolecular β-sheet conformation and contain inner amyloid-like fibrillar structure. In addition, despite their ordered structure, HNRPDL IBs are highly neurotoxic. - Conclusions: our results suggest that at least some of the disorders caused by the aggregation of human prion-like proteins would rely on the formation of classical amyloid assemblies rather than being caused by amorphous aggregates. They also illustrate the power of microbial cell factories to model amyloid aggregation.
Nota: Salvador Ventura is supported by SOE4/P1/E831 grant from SUDOE. INTERREG IV B. EUROPEAN UNION. SV is supported by ICREA Academia 2009
Nota: Número d'acord de subvenció MINECO/BFU2013-44763-P
Drets: Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. Creative Commons
Llengua: Anglès
Document: article ; recerca ; publishedVersion
Matèria: Inclusion bodies ; Bacteria ; Amyloid ; Prions ; Prion-like domains ; Heterogeneous ribonucleoproteins ; Neurodegenerative disorders
Publicat a: Microbial cell factories, Vol. 14 (2015) , art. 102, ISSN 1475-2859

DOI: 10.1186/s12934-015-0284-7
PMID: 26160665


14 p, 3.5 MB

El registre apareix a les col·leccions:
Documents de recerca > Documents dels grups de recerca de la UAB > Centres i grups de recerca (producció científica) > Ciències de la salut i biociències > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Articles de recerca
Articles > Articles publicats

 Registre creat el 2020-06-22, darrera modificació el 2021-05-05



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