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WNK kinases sense molecular crowding and rescue cell volume via phase separation.
Boyd-Shiwarski, Cary R; Shiwarski, Daniel J; Griffiths, Shawn E; Beacham, Rebecca T; Norrell, Logan; Morrison, Daryl E; Wang, Jun; Mann, Jacob; Tennant, William; Anderson, Eric N; Franks, Jonathan; Calderon, Michael; Connolly, Kelly A; Cheema, Muhammad Umar; Weaver, Claire J; Nkashama, Lubika J; Weckerly, Claire C; Querry, Katherine E; Pandey, Udai Bhan; Donnelly, Christopher J; Sun, Dandan; Rodan, Aylin R; Subramanya, Arohan R.
Afiliación
  • Boyd-Shiwarski CR; Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Pittsburgh Center for Kidney Research, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  • Shiwarski DJ; Department of Biomedical Engineering, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
  • Griffiths SE; Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  • Beacham RT; Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  • Norrell L; Molecular Medicine Program, University of Utah, Salt Lake City, UT 84132, USA.
  • Morrison DE; Molecular Medicine Program, University of Utah, Salt Lake City, UT 84132, USA.
  • Wang J; Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  • Mann J; Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  • Tennant W; Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  • Anderson EN; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  • Franks J; Center for Biological Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  • Calderon M; Center for Biological Imaging, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  • Connolly KA; Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  • Cheema MU; Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  • Weaver CJ; Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  • Nkashama LJ; Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  • Weckerly CC; Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  • Querry KE; Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  • Pandey UB; Department of Pediatrics, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Center for Protein Conformational Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  • Donnelly CJ; Department of Neurobiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Center for Protein Conformational Diseases, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA.
  • Sun D; Department of Neurology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; VA Pittsburgh Healthcare System, Pittsburgh, PA 15240, USA.
  • Rodan AR; Department of Human Genetics, University of Utah, Salt Lake City, UT 84132, USA; Molecular Medicine Program, University of Utah, Salt Lake City, UT 84132, USA; Department of Internal Medicine, Division of Nephrology and Hypertension, University of Utah, Salt Lake City, UT 84132, USA; Medical Service
  • Subramanya AR; Department of Medicine, Renal-Electrolyte Division, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261, USA; Center for Protein Conformational Diseases, University of Pittsburgh School
Cell ; 185(24): 4488-4506.e20, 2022 11 23.
Article en En | MEDLINE | ID: mdl-36318922
When challenged by hypertonicity, dehydrated cells must recover their volume to survive. This process requires the phosphorylation-dependent regulation of SLC12 cation chloride transporters by WNK kinases, but how these kinases are activated by cell shrinkage remains unknown. Within seconds of cell exposure to hypertonicity, WNK1 concentrates into membraneless condensates, initiating a phosphorylation-dependent signal that drives net ion influx via the SLC12 cotransporters to restore cell volume. WNK1 condensate formation is driven by its intrinsically disordered C terminus, whose evolutionarily conserved signatures are necessary for efficient phase separation and volume recovery. This disorder-encoded phase behavior occurs within physiological constraints and is activated in vivo by molecular crowding rather than changes in cell size. This allows kinase activity despite an inhibitory ionic milieu and permits cell volume recovery through condensate-mediated signal amplification. Thus, WNK kinases are physiological crowding sensors that phase separate to coordinate a cell volume rescue response.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Serina-Treonina Quinasas Idioma: En Revista: Cell Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proteínas Serina-Treonina Quinasas Idioma: En Revista: Cell Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos