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The perinuclear region concentrates disordered proteins with predicted phase separation distributed in a 3D network of cytoskeletal filaments and organelles.
do Amaral, Mariana Juliani; de Andrade Rosa, Ivone; Andrade, Sarah Azevedo; Fang, Xi; Andrade, Leonardo Rodrigues; Costa, Manoel Luis; Mermelstein, Claudia.
Afiliação
  • do Amaral MJ; Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, RJ, Brazil.
  • de Andrade Rosa I; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, RJ, Brazil.
  • Andrade SA; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, RJ, Brazil.
  • Fang X; Department of Medicine, University of California, La Jolla, CA, USA.
  • Andrade LR; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, RJ, Brazil; Salk Institute for Biological Studies, Waitt Advanced Biophotonics Core, La Jolla, CA, USA.
  • Costa ML; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, RJ, Brazil.
  • Mermelstein C; Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, RJ, Brazil. Electronic address: mermelstein@ufrj.br.
Biochim Biophys Acta Mol Cell Res ; 1869(1): 119161, 2022 01.
Article em En | MEDLINE | ID: mdl-34655689
Membraneless organelles have emerged during the evolution of eukaryotic cells as intracellular domains in which multiple proteins organize into complex structures to perform specialized functions without the need of a lipid bilayer compartment. Here we describe the perinuclear space of eukaryotic cells as a highly organized network of cytoskeletal filaments that facilitates assembly of biomolecular condensates. Using bioinformatic analyses, we show that the perinuclear proteome is enriched in intrinsic disorder with several proteins predicted to undergo liquid-liquid phase separation. We also analyze immunofluorescence and transmission electron microscopy images showing the association between the nucleus and other organelles, such as mitochondria and lysosomes, or the labeling of specific proteins within the perinuclear region of cells. Altogether our data support the existence of a perinuclear dense sub-micron region formed by a well-organized three-dimensional network of structural and signaling proteins, including several proteins containing intrinsically disordered regions with phase behavior. This network of filamentous cytoskeletal proteins extends a few micrometers from the nucleus, contributes to local crowding, and organizes the movement of molecular complexes within the perinuclear space. Our findings take a key step towards understanding how membraneless regions within eukaryotic cells can serve as hubs for biomolecular condensates assembly, in particular the perinuclear space. Finally, evaluation of the disease context of the perinuclear proteins revealed that alterations in their expression can lead to several pathological conditions, and neurological disorders and cancer are among the most frequent.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Citoesqueleto de Actina / Membrana Nuclear Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Revista: Biochim Biophys Acta Mol Cell Res Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Citoesqueleto de Actina / Membrana Nuclear Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals Idioma: En Revista: Biochim Biophys Acta Mol Cell Res Ano de publicação: 2022 Tipo de documento: Article País de afiliação: Brasil País de publicação: Holanda