Your browser doesn't support javascript.
loading
Cytosolic condensates rich in polyserine define subcellular sites of tau aggregation.
Lester, Evan; Van Alstyne, Meaghan; McCann, Kathleen L; Reddy, Spoorthy; Cheng, Li Yi; Kuo, Jeff; Pratt, James; Parker, Roy.
Afiliação
  • Lester E; Medical Scientist Training Program, University of Colorado Anschutz Medical Campus, Aurora, CO 80045.
  • Van Alstyne M; Department of Biochemistry, University of Colorado, Boulder, CO 80303.
  • McCann KL; Department of Biochemistry, University of Colorado, Boulder, CO 80303.
  • Reddy S; HHMI, University of Colorado, Boulder, CO 80303.
  • Cheng LY; Department of Biochemistry, University of Colorado, Boulder, CO 80303.
  • Kuo J; HHMI, University of Colorado, Boulder, CO 80303.
  • Pratt J; Department of Biochemistry, University of Colorado, Boulder, CO 80303.
  • Parker R; Department of Biochemistry, University of Colorado, Boulder, CO 80303.
Proc Natl Acad Sci U S A ; 120(3): e2217759120, 2023 01 17.
Article em En | MEDLINE | ID: mdl-36626563
Tau aggregates are a hallmark of multiple neurodegenerative diseases and can contain RNAs and RNA-binding proteins, including serine/arginine repetitive matrix protein 2 (SRRM2) and pinin (PNN). However, how these nuclear proteins mislocalize and their influence on the prion-like propagation of tau aggregates is unknown. We demonstrate that polyserine repeats in SRRM2 and PNN are necessary and sufficient for recruitment to tau aggregates. Moreover, we show tau aggregates preferentially grow in association with endogenous cytoplasmic assemblies-mitotic interchromatin granules and cytoplasmic speckles (CSs)-which contain SRRM2 and PNN. Polyserine overexpression in cells nucleates assemblies that are sites of tau aggregate growth. Further, modulating the levels of polyserine-containing proteins results in a corresponding change in tau aggregation. These findings define a specific protein motif, and cellular condensates, that promote tau aggregate propagation. As CSs form in induced pluripotent stem cell (iPSC) derived neurons under inflammatory or hyperosmolar stress, they may affect tau aggregate propagation in neurodegenerative disease.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Neurodegenerativas / Tauopatias / Doença de Alzheimer Limite: Humans Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Doenças Neurodegenerativas / Tauopatias / Doença de Alzheimer Limite: Humans Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2023 Tipo de documento: Article