德国马普研究所Martin J. Lohse、Andreas Bock等研究人员合作实现在纳米尺度下cAMP信号的光学成像。2020年8月25日，国际知名学术期刊《细胞》在线发表了这一成果。
Title: Optical Mapping of cAMP Signaling at the Nanometer Scale
Author: Andreas Bock, Paolo Annibale, Charlotte Konrad, Annette Hannawacker, Selma E. Anton, Isabella Maiellaro, Ulrike Zabel, Sivaraj Sivaramakrishnan, Martin Falcke, Martin J. Lohse
Issue&Volume: 2020-08-25
Abstract: Cells relay a plethora of extracellular signals to specific cellular responses byusing only a few second messengers, such as cAMP. To explain signaling specificity,cAMP-degrading phosphodiesterases (PDEs) have been suggested to confine cAMP to distinctcellular compartments. However, measured rates of fast cAMP diffusion and slow PDEactivity render cAMP compartmentalization essentially impossible. Using fluorescencespectroscopy, we show that, contrary to earlier data, cAMP at physiological concentrationsis predominantly bound to cAMP binding sites and, thus, immobile. Binding and unbindingresults in largely reduced cAMP dynamics, which we term “buffered diffusion.” Witha large fraction of cAMP being buffered, PDEs can create nanometer-size domains oflow cAMP concentrations. Using FRET-cAMP nanorulers, we directly map cAMP gradientsat the nanoscale around PDE molecules and the areas of resulting downstream activationof cAMP-dependent protein kinase (PKA). Our study reveals that spatiotemporal cAMPsignaling is under precise control of nanometer-size domains shaped by PDEs that gateactivation of downstream effectors.
DOI: 10.1016/j.cell.2020.07.035
Source: https://www.cell.com/cell/fulltext/S0092-8674(20)30943-0