Optical Mapping of cAMP Signaling at the Nanometer Scale.
Optical Mapping of cAMP Signaling at the Nanometer Scale.
复制标题
在纳米尺度上的cAMP信号传导的光学映射。
DOI：
10.1016/j.cell.2020.07.035
复制
发表时间：
2020-09-17
期刊：
影响因子：
64.5
通讯作者：
Lohse MJ
中科院分区：
文献类型：
--
作者：
Bock A;Annibale P;Konrad C;Hannawacker A;Anton SE;Maiellaro I;Zabel U;Sivaramakrishnan S;Falcke M;Lohse MJ
Cells relay a plethora of extracellular signals to specific cellular responses 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-sized 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-sized domains shaped by PDEs that gate the activation of downstream effectors.
登录
查看更多内容
DOI：
10.1073/pnas.1222097110
发表时间：
2013-07-23
影响因子：
11.1
作者：
Di Rienzo, Carmine;Gratton, Enrico;Cardarelli, Francesco
通讯作者：
Cardarelli, Francesco
影响因子：
48
作者：
Gibson, Daniel G.;Young, Lei;Smith, Hamilton O.
通讯作者：
Smith, Hamilton O.
影响因子：
3.4
作者：
Chen, CH;Nakamura, T;Koutalos, Y
通讯作者：
Koutalos, Y
影响因子：
20.1
作者：
Nikolaev, Viacheslav O.;Buenemann, Moritz;Engelhardt, Stefan
通讯作者：
Engelhardt, Stefan
影响因子：
--
作者：
Depry, Charlene;Allen, Michael D.;Zhang, Jin
通讯作者：
Zhang, Jin