Li Y, Goldbeter A
Faculté des Sciences, Université Libre de Bruxelles, Belgium.
J Theor Biol. 1990 Oct 7;146(3):355-67. doi: 10.1016/s0022-5193(05)80746-5.
Dictyostelium discoideum amoebae represent a prototype for the study of periodic signaling in intercellular communication. These cells synthesize cAMP in response to cAMP pulses. Cell responsiveness in Dictyostelium can be characterized by the capability to generate a large number of significant responses to cAMP signals in a given amount of time. The existence of a frequency of pulsatile cAMP signals yielding maximum responsiveness is demonstrated by analysis of a realistic model for cAMP synthesis, based on receptor desensitization. The optimal frequency of stimulation closely depends on the kinetics of receptor desensitization and resensitization in target cells. Synthesis of cAMP is determined both in conditions where cells are not excitable and in conditions where they relay suprathreshold pulses of cAMP. Moreover, the effect of the stimulus waveform is investigated, and several measures of cell responsiveness are compared. The results provide an explanation for the effectiveness of cAMP pulses delivered at 5 min intervals, and for the failure of pulses delivered at 2 min intervals, in inducing slime mold development. Besides applying to intercellular communication in Dictyostelium, the present analysis bears on patterns of pulsatile signaling observed for hormones and growth factors. In all these cases, it appears that pulsatile signals can be encoded in terms of their frequency on the basis of desensitization in target cells.
盘基网柄菌变形虫是研究细胞间通讯中周期性信号传导的一个原型。这些细胞会响应cAMP脉冲而合成cAMP。盘基网柄菌中的细胞反应性可通过在给定时间内对cAMP信号产生大量显著反应的能力来表征。基于受体脱敏作用，通过对cAMP合成的一个现实模型进行分析，证明了存在产生最大反应性的脉动cAMP信号频率。刺激的最佳频率密切依赖于靶细胞中受体脱敏和再敏化的动力学。cAMP的合成在细胞不可兴奋的条件下以及在它们传递超阈值cAMP脉冲的条件下都能被确定。此外，还研究了刺激波形的影响，并比较了几种细胞反应性的测量方法。这些结果解释了以5分钟间隔传递的cAMP脉冲在诱导黏菌发育方面的有效性，以及以2分钟间隔传递的脉冲在诱导黏菌发育方面的失败原因。除了应用于盘基网柄菌中的细胞间通讯外，目前的分析还涉及到在激素和生长因子中观察到的脉动信号传导模式。在所有这些情况下，似乎脉动信号可以基于靶细胞中的脱敏作用，根据其频率进行编码。
