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猫视觉皮层蛋白质(特别是微管相关蛋白2,即MAP 2)的环磷酸腺苷刺激的磷酸化的个体发育变化:正常饲养和暗饲养以及光照暴露的影响

Ontogenetic changes in the cyclic adenosine 3',5'-monophosphate-stimulatable phosphorylation of cat visual cortex proteins, particularly of microtubule-associated protein 2 (MAP 2): effects of normal and dark rearing and of the exposure to light.

作者信息

Aoki C, Siekevitz P

出版信息

J Neurosci. 1985 Sep;5(9):2465-83. doi: 10.1523/JNEUROSCI.05-09-02465.1985.

Abstract

Based on a theory that a norepinephrine-stimulated cascade of events resulting in an increase of intracellular cyclic adenosine 3',5'-monophosphate (cAMP) modulates the state of plasticity for the receptive field property of visual cortical neurons, we have followed the ontogenetic changes in cAMP-stimulated phosphorylation of proteins in whole homogenates obtained from developing visual cortices of cats. In vitro phosphorylation was assayed with and without cAMP and the cAMP-dependent protein kinase, and the phosphoproteins separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis were counted for 32P incorporated from [gamma-32P]ATP. It was found that the regulatory subunits of the cAMP-dependent protein kinase are present and fully active by birth, whereas the synapsin content increases at a rate concomitant with synaptogenesis. These ontogenetic developments are not influenced by dark rearing (DR) from birth, a procedure which postpones the onset of the critical period (CP) for plasticity. By contrast, the cAMP-stimulatable phosphorylation of microtubule-associated protein 2 (MAP 2), which under normal rearing conditions increases from birth to the second month, is strongly modulated by the presence of light in the environment. After DR for various periods, kittens were subsequently exposed to light so as to trigger the onset of the CP that had been postponed. A few hours of light were sufficient to cause a large increase in the in vitro phosphorylation of MAP 2. This effect is not observed in the auditory cortex or the lateral geniculate nucleus of the same animals, or in the visual cortex of normally reared cats which were then dark reared in adulthood. But this effect was seen in the visual cortices of cats following 5 months of DR from birth, animals which by chronological age have passed the CP, presumably because the onset of the CP was extended by the DR procedure. The cAMP-dependent phosphorylation of MAP 2 (and its dephosphorylation) may be an important factor for determining the state of plasticity in the CP through its affecting the dendritic cytoskeletal organization involving tubulin and actin.

摘要

基于一种理论,即去甲肾上腺素刺激引发的一系列事件导致细胞内环磷酸腺苷(cAMP)增加,从而调节视觉皮层神经元感受野特性的可塑性状态,我们追踪了从发育中的猫视觉皮层获取的全匀浆中cAMP刺激的蛋白质磷酸化的个体发育变化。在有或没有cAMP及cAMP依赖性蛋白激酶的情况下测定体外磷酸化,通过十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳分离磷酸化蛋白,并对从[γ-32P]ATP掺入的32P进行计数。发现cAMP依赖性蛋白激酶的调节亚基在出生时就已存在且完全有活性,而突触素含量的增加速率与突触发生同步。这些个体发育过程不受出生后黑暗饲养(DR)的影响,黑暗饲养会推迟可塑性关键期(CP)的开始。相比之下,在正常饲养条件下从出生到第二个月增加的微管相关蛋白2(MAP 2)的cAMP可刺激的磷酸化,受到环境中光照的强烈调节。在不同时间段进行黑暗饲养后,小猫随后暴露于光线下以触发已被推迟的关键期的开始。几小时的光照足以使MAP 2的体外磷酸化大幅增加。在同一动物的听觉皮层或外侧膝状体核中未观察到这种效应,在成年后进行黑暗饲养的正常饲养猫的视觉皮层中也未观察到这种效应。但在出生后进行5个月黑暗饲养的猫的视觉皮层中观察到了这种效应,按年龄这些动物应该已经度过了关键期,推测是因为黑暗饲养程序延长了关键期的开始时间。MAP 2的cAMP依赖性磷酸化(及其去磷酸化)可能是通过影响涉及微管蛋白和肌动蛋白的树突细胞骨架组织来决定关键期可塑性状态的一个重要因素。

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