PROTEIN-SYNTHESIS DURING ACQUISITION OF LONG-TERM FACILITATION IS NEEDED FOR THE PERSISTENT LOSS OF REGULATORY SUBUNITS OF THE APLYSIA CAMP-DEPENDENT PROTEIN-KINASE
PROTEIN-SYNTHESIS DURING ACQUISITION OF LONG-TERM FACILITATION IS NEEDED FOR THE PERSISTENT LOSS OF REGULATORY SUBUNITS OF THE APLYSIA CAMP-DEPENDENT PROTEIN-KINASE
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DOI：
10.1073/pnas.87.10.3788
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发表时间：
1990-05-01
影响因子：
11.1
通讯作者：
SCHWARTZ, JH
中科院分区：
文献类型：
--
作者：
BERGOLD, PJ;SWEATT, JD;SCHWARTZ, JH
根据暴露的数量或时间长短，血清素的应用可以对海兔感觉运动突触产生短期或长期的突触前促进作用。 cAMP 依赖性蛋白激酶是两个调节亚基和两个催化亚基的异二聚体，已被证明只有在长期促进过程中才能稳定激活。茴香霉素是海兔中一种有效、可逆、特异性的蛋白质合成抑制剂，可阻断激酶的长期促进和持续激活。我们在此报告，胸膜感觉细胞暴露于血清素 2 小时会降低调节亚基的浓度，但不会改变催化亚基的浓度，如 24 小时后测定的那样；接触血清素 5 分钟对任何一种亚基都没有影响。使用可渗透的 cAMP 类似物以及磷酸二酯酶抑制剂异丁基甲基黄嘌呤来增加细胞内 cAMP 也会减少调节亚基，表明 cAMP 是介导血清素作用的第二信使。仅当与血清素一起使用时，茴香霉素才能阻止调节亚基的丢失。血清素治疗 2 小时后应用没有效果。在海兔副齿舌收缩肌中，长时间暴露于血清素或肽递质小心肌活性肽 B（两者都会导致细胞内 cAMP 大幅增加）不会减少调节亚基。因此，这种调节 cAMP 依赖性蛋白激酶的机制可能是神经系统特有的。我们得出的结论是，在长期促进过程中，新的蛋白质是响应促进刺激而合成的，这改变了 cAMP 依赖性蛋白激酶亚基的比例。这种比例的改变可以持续激活激酶并产生在长期促进的感觉细胞中看到的持续磷酸化。
Depending on the number or the length of exposure, application of serotonin can produce either short-term or long-term presynaptic facilitation of Aplysia sensory-to-motor synapses. The cAMP-dependent protein kinase, a heterodimer of two regulatory and two catalytic subunits, has been shown to become stably activated only during long-term facilitation. Both acquisition of long-term facilitation and persistent activation of the kinase is blocked by anisomycin, an effective, reversible, and specific inhibitor of protein synthesis in Aplysia. We report here that 2-hr exposure of pleural sensory cells to serotonin lowers the concentration of regulatory subunits but does not change the concentration of catalytic subunits, as assayed 24 hr later; 5-min exposure to serotonin has no effect on either type of subunit. Increasing intracellular cAMP with a permeable analog of cAMP together with the phosphodiesterase inhibitor isobutyl methylxanthine also decreased regulatory subunits, suggesting that cAMP is the second messenger mediating serotonin action. Anisomycin blocked the loss of regulatory subunits only when applied with serotonin; application after the 2-hr treatment with serotonin had no effect. In the Aplysia accessory radula contractor muscle, prolonged exposure to serotonin or to the peptide transmitter small cardioactive peptide B, both of which produce large increases in intracellular cAMP, does not decrease regulatory subunits. This mechanism of regulating the cAMP-dependent protein kinase therefore may be specific to the nervous system. We conclude that during long-term facilitation, new protein is syntehsized in response to the facilitatory stimulus, which changes the ratio of subunits of the cAMP-dependent protein kinase. This alteration in ratio could persistently activate the kinase and produce the persistent phosphorylation seen in long-term facilitated sensory cells.