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Optical Mapping of cAMP Signaling at the Nanometer Scale.
Bock, Andreas; Annibale, Paolo; Konrad, Charlotte; Hannawacker, Annette; Anton, Selma E; Maiellaro, Isabella; Zabel, Ulrike; Sivaramakrishnan, Sivaraj; Falcke, Martin; Lohse, Martin J.
Afiliación
  • Bock A; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Str. 10, 13125 Berlin, Germany; Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Germany. Electronic address: andreas.bock@mdc-berlin.de.
  • Annibale P; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Str. 10, 13125 Berlin, Germany; Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Germany.
  • Konrad C; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Str. 10, 13125 Berlin, Germany; Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Germany.
  • Hannawacker A; Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Germany.
  • Anton SE; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Str. 10, 13125 Berlin, Germany; Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Germany.
  • Maiellaro I; Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Germany.
  • Zabel U; Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Germany.
  • Sivaramakrishnan S; Department of Genetics, Cell Biology, and Development, University of Minnesota, Minneapolis, MN 55455, USA.
  • Falcke M; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Str. 10, 13125 Berlin, Germany; Department of Physics, Humboldt University, Newtonstr. 15, 12489 Berlin, Germany.
  • Lohse MJ; Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Robert-Rössle-Str. 10, 13125 Berlin, Germany; Institute of Pharmacology and Toxicology, University of Würzburg, Versbacher Str. 9, 97078 Würzburg, Germany; Institute for Chemistry and Biochemistry, Free University, Takustr. 3,
Cell ; 182(6): 1519-1530.e17, 2020 09 17.
Article en En | MEDLINE | ID: mdl-32846156
Cells relay a plethora of extracellular signals to specific cellular responses by using only a few second messengers, such as cAMP. To explain signaling specificity, cAMP-degrading phosphodiesterases (PDEs) have been suggested to confine cAMP to distinct cellular compartments. However, measured rates of fast cAMP diffusion and slow PDE activity render cAMP compartmentalization essentially impossible. Using fluorescence spectroscopy, we show that, contrary to earlier data, cAMP at physiological concentrations is predominantly bound to cAMP binding sites and, thus, immobile. Binding and unbinding results in largely reduced cAMP dynamics, which we term "buffered diffusion." With a large fraction of cAMP being buffered, PDEs can create nanometer-size domains of low cAMP concentrations. Using FRET-cAMP nanorulers, we directly map cAMP gradients at the nanoscale around PDE molecules and the areas of resulting downstream activation of cAMP-dependent protein kinase (PKA). Our study reveals that spatiotemporal cAMP signaling is under precise control of nanometer-size domains shaped by PDEs that gate activation of downstream effectors.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Transducción de Señal / Proteínas Quinasas Dependientes de AMP Cíclico / AMP Cíclico / Hidrolasas Diéster Fosfóricas / Análisis de la Célula Individual Límite: Humans Idioma: En Revista: Cell Año: 2020 Tipo del documento: Article

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Transducción de Señal / Proteínas Quinasas Dependientes de AMP Cíclico / AMP Cíclico / Hidrolasas Diéster Fosfóricas / Análisis de la Célula Individual Límite: Humans Idioma: En Revista: Cell Año: 2020 Tipo del documento: Article