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The Parkinson's disease protein alpha-synuclein is a modulator of processing bodies and mRNA stability.
Hallacli, Erinc; Kayatekin, Can; Nazeen, Sumaiya; Wang, Xiou H; Sheinkopf, Zoe; Sathyakumar, Shubhangi; Sarkar, Souvarish; Jiang, Xin; Dong, Xianjun; Di Maio, Roberto; Wang, Wen; Keeney, Matthew T; Felsky, Daniel; Sandoe, Jackson; Vahdatshoar, Aazam; Udeshi, Namrata D; Mani, D R; Carr, Steven A; Lindquist, Susan; De Jager, Philip L; Bartel, David P; Myers, Chad L; Greenamyre, J Timothy; Feany, Mel B; Sunyaev, Shamil R; Chung, Chee Yeun; Khurana, Vikram.
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  • Hallacli E; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Whitehead Institute for Biomedical Resea
  • Kayatekin C; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
  • Nazeen S; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Department of Biomedical Informatics, Ha
  • Wang XH; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Sheinkopf Z; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Sathyakumar S; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Sarkar S; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Jiang X; Yumanity Therapeutics, Boston, MA 02135, USA.
  • Dong X; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Genomics and Bioinformatics Hub, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Researc
  • Di Maio R; Pittsburgh Institute for Neurodegenerative Diseases and Department of Neurology, Pittsburgh, PA 15213, USA.
  • Wang W; Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
  • Keeney MT; Pittsburgh Institute for Neurodegenerative Diseases and Department of Neurology, Pittsburgh, PA 15213, USA.
  • Felsky D; Krembil Centre for Neuroinformatics and Department of Psychiatry, University of Toronto, Toronto, ON M5T 1R8, Canada; Department of Psychiatry, Temerty Faculty of Medicine, University of Toronto, 1 King's College Circle, Toronto, ON M5S 1A8, Canada; Division of Biostatistics, Dalla Lana School of Pu
  • Sandoe J; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
  • Vahdatshoar A; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Udeshi ND; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Mani DR; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Carr SA; Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • Lindquist S; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Cambridge, MA 02142, USA; Department of Biology, MIT, Cambridge, MA 02139, USA.
  • De Jager PL; Center for Translational & Computational Neuroimmunology, Department of Neurology, Columbia University Irving Medical Center, New York, NY 10032, USA.
  • Bartel DP; Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA; Howard Hughes Medical Institute, Cambridge, MA 02142, USA; Department of Biology, MIT, Cambridge, MA 02139, USA.
  • Myers CL; Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
  • Greenamyre JT; Pittsburgh Institute for Neurodegenerative Diseases and Department of Neurology, Pittsburgh, PA 15213, USA.
  • Feany MB; Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA.
  • Sunyaev SR; Department of Biomedical Informatics, Harvard Medical School, Boston, MA 02115, USA; Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115.
  • Chung CY; Yumanity Therapeutics, Boston, MA 02135, USA.
  • Khurana V; Ann Romney Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Division of Movement Disorders, Department of Neurology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02115, USA; Aligning Science Across Parkinson's (ASA
Cell ; 185(12): 2035-2056.e33, 2022 06 09.
Article en En | MEDLINE | ID: mdl-35688132
ABSTRACT
Alpha-synuclein (αS) is a conformationally plastic protein that reversibly binds to cellular membranes. It aggregates and is genetically linked to Parkinson's disease (PD). Here, we show that αS directly modulates processing bodies (P-bodies), membraneless organelles that function in mRNA turnover and storage. The N terminus of αS, but not other synucleins, dictates mutually exclusive binding either to cellular membranes or to P-bodies in the cytosol. αS associates with multiple decapping proteins in close proximity on the Edc4 scaffold. As αS pathologically accumulates, aberrant interaction with Edc4 occurs at the expense of physiologic decapping-module interactions. mRNA decay kinetics within PD-relevant pathways are correspondingly disrupted in PD patient neurons and brain. Genetic modulation of P-body components alters αS toxicity, and human genetic analysis lends support to the disease-relevance of these interactions. Beyond revealing an unexpected aspect of αS function and pathology, our data highlight the versatility of conformationally plastic proteins with high intrinsic disorder.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Alfa-Sinucleína Límite: Humans Idioma: En Revista: Cell Año: 2022 Tipo del documento: Article
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Enfermedad de Parkinson / Alfa-Sinucleína Límite: Humans Idioma: En Revista: Cell Año: 2022 Tipo del documento: Article