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Mechanisms for localising calcineurin and CaMKII in dendritic spines
Cellular Signalling ( IF 4.4 ) Pub Date : 2018-05-27 , DOI: 10.1016/j.cellsig.2018.05.010
Christopher J. Penny , Matthew G. Gold

Calcineurin and calmodulin-dependent protein kinase II (CaMKII) are both highly abundant in neurons, and both are activated by calmodulin at similar Ca2+ concentrations in the test tube. However, they fulfill opposite functions in dendritic spines, with CaMKII activity driving long-term synaptic potentiation following large influxes of Ca2+ through NMDA-type glutamate receptors (NMDARs), and calcineurin responding to smaller influxes of Ca2+ through the same receptors to induce long-term depression. In this review, we explore the notion that precise dynamic localisation of the two enzymes at different sites within dendritic spines is fundamental to this behaviour. We describe the structural basis of calcineurin and CaMKII localisation by their interaction with proteins including AKAP79, densin-180, α-actinin, and NMDARs. We then consider how interactions with these proteins likely position calcineurin and CaMKII at different distances from Ca2+ microdomains emanating from the mouths of NMDARs in order to drive the divergent responses. We also highlight shortcomings in our current understanding of synaptic localisation of these two important signalling enzymes.



中文翻译:

钙调神经磷酸酶和CaMKII在树突棘中的定位机制

钙调神经磷酸酶和钙调蛋白依赖性蛋白激酶II(CaMKII)都在神经元中高度丰富,并且在试管中均以类似的Ca 2+浓度被钙调蛋白激活。然而,它们在树突棘中执行相反的功能,CaMKII活性通过NMDA型谷氨酸受体(NMDAR)大量流入Ca 2+后驱动长期突触增强,而钙调神经磷酸酶响应较小的Ca 2+流入。通过相同的受体诱发长期抑郁。在这篇综述中,我们探讨了两种酶在树突棘内不同部位的精确动态定位是这种行为的基础的观点。我们通过其与包括AKAP79,densin-180,α-actinin和NMDARs的蛋白质相互作用来描述钙调神经磷酸酶和CaMKII定位的结构基础。然后,我们考虑与这些蛋白质的相互作用如何可能将钙调神经磷酸酶和CaMKII定位在与从NMDAR口发出的Ca 2+微结构域不同的距离上,以驱动发散反应。在我们目前对这两种重要信号酶的突触定位的理解中,我们还强调了缺点。

更新日期:2018-05-27
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