PKCα integrates spatiotemporally distinct Ca(2+) and autocrine BDNF signaling to facilitate synaptic plasticity.
PKCα integrates spatiotemporally distinct Ca(2+) and autocrine BDNF signaling to facilitate synaptic plasticity.
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DOI：
10.1038/s41593-018-0184-3
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发表时间：
2018-08
影响因子：
25
通讯作者：
Yasuda R
中科院分区：
文献类型：
--
作者：
Colgan LA;Hu M;Misler JA;Parra-Bueno P;Moran CM;Leitges M;Yasuda R
蛋白激酶C（PKC）酶早已被确立为突触可塑性的关键。然而，它是未知的钙依赖性PKC同工酶是否激活树突棘在可塑性，如果是这样的话，这种突触活动是如何编码的PKC。在这里，我们使用新开发的同工酶特异性传感器，证明经典同工酶被不同程度地激活并具有独特的动力学。PKCα在刺激的脊髓中被强烈而迅速地激活，并且是结构可塑性所需的唯一同工酶。这种特异性依赖于仅存在于PKCα中的PDZ结合结构域。可塑性过程中PKCα的激活需要NMDAR Ca 2+流和自分泌BDNF-TrkB信号，这两种信号途径在时空尺度上有很大差异。我们的研究结果表明，通过整合这些信号，PKCα结合了最近的，附近的突触可塑性与局部突触输入的措施，使复杂的细胞计算，如有效的突触依赖性学习所必需的可塑性异突触促进。
The Protein Kinase C (PKC) enzymes have long been established as critical for synaptic plasticity. However, it is unknown whether Ca2+-dependent PKC isozymes are activated in dendritic spines during plasticity, and if so, how this synaptic activity is encoded by PKC. Here, using newly-developed, isozyme-specific sensors, we demonstrate that classic isozymes are activated to varying degrees and with unique kinetics. PKCα is activated robustly and rapidly in stimulated spines and is the only isozyme required for structural plasticity. This specificity, depends on a PDZ-binding domain present only in PKCα. The activation of PKCα during plasticity requires both NMDAR Ca2+-flux and autocrine BDNF-TrkB signaling, two pathways that differ vastly in their spatiotemporal scales of signaling. Our results suggest that by integrating these signals, PKCα combines a measure of recent, nearby synaptic plasticity with local synaptic input, enabling complex cellular computations such as heterosynaptic facilitation of plasticity necessary for efficient hippocampal-dependent learning.
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影响因子：
64.8
作者：
Hayashi-Takagi A;Yagishita S;Nakamura M;Shirai F;Wu YI;Loshbaugh AL;Kuhlman B;Hahn KM;Kasai H
通讯作者：
Kasai H
影响因子：
64.8
作者：
Hedrick NG;Harward SC;Hall CE;Murakoshi H;McNamara JO;Yasuda R
通讯作者：
Yasuda R
影响因子：
64.5
作者：
ABELIOVICH, A;CHEN, C;TONEGAWA, S
通讯作者：
TONEGAWA, S
影响因子：
5.3
作者：
Apolloni, A;Prior, IA;Hancock, JF
通讯作者：
Hancock, JF
DOI：
10.1073/pnas.0709311104
发表时间：
2007-12-04
影响因子：
11.1
作者：
Hongpaisan, Jarin;Alkon, Daniel L.
通讯作者：
Alkon, Daniel L.