The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility.
The MK2/3 cascade regulates AMPAR trafficking and cognitive flexibility.
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DOI：
10.1038/ncomms5701
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发表时间：
2014-08-19
影响因子：
16.6
通讯作者：
Correa, Sonia A. L.
中科院分区：
文献类型：
--
作者：
Eales, Katherine L.;Palygin, Oleg;O'Loughlin, Thomas;Rasooli-Nejad, Seyed;Gaestel, Matthias;Mueller, Juergen;Collins, Dawn R.;Pankratov, Yuriy;Correa, Sonia A. L.
长时程增强和长时程抑制（LTD）之间的相互作用被认为涉及学习和记忆的形成。在海马中表达的LTD的一种形式是由第1组代谢型谷氨酸受体（mGluR）的激活引发的。重要的是，mGluRs已被证明对获得新记忆和逆转学习至关重要，这些过程被认为对认知灵活性至关重要。在这里，我们提供的证据表明，MAPK激活的蛋白激酶2和3（MK 2/3）调节神经元的棘形态，突触传递和可塑性。此外，mGluR-LTD在MK 2/3双敲除（DKO）小鼠的海马中受损，这一观察结果反映了GluA 1亚基内吞作用的缺陷。与受损的mGluR-LTD一致，MK 2/3 DKO小鼠在海马依赖性空间逆转学习中具有明显的缺陷。这些新的发现表明，MK2/3级联在控制突触可塑性和认知中起着战略性作用。 MK2/3激酶在大脑的海马和皮质中都高度表达，但它们的作用尚不清楚。Eales等人在这里表明，MK2/3信号调节树突棘形态，并通过调节AMPA受体运输和认知过程来调节突触可塑性。
The interplay between long-term potentiation and long-term depression (LTD) is thought to be involved in learning and memory formation. One form of LTD expressed in the hippocampus is initiated by the activation of the group 1 metabotropic glutamate receptors (mGluRs). Importantly, mGluRs have been shown to be critical for acquisition of new memories and for reversal learning, processes that are thought to be crucial for cognitive flexibility. Here we provide evidence that MAPK-activated protein kinases 2 and 3 (MK2/3) regulate neuronal spine morphology, synaptic transmission and plasticity. Furthermore, mGluR-LTD is impaired in the hippocampus of MK2/3 double knockout (DKO) mice, an observation that is mirrored by deficits in endocytosis of GluA1 subunits. Consistent with compromised mGluR-LTD, MK2/3 DKO mice have distinctive deficits in hippocampal-dependent spatial reversal learning. These novel findings demonstrate that the MK2/3 cascade plays a strategic role in controlling synaptic plasticity and cognition. MK2/3 kinases are both highly expressed in the hippocampus and cortex of the brain, but their role is unclear. Here Eales et al. show that MK2/3 signalling regulates dendritic spine morphology and is required for synaptic plasticity via the regulation of AMPA receptor trafficking, and cognitive processes.
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影响因子：
9.8
作者：
Lalo U;Palygin O;Rasooli-Nejad S;Andrew J;Haydon PG;Pankratov Y
通讯作者：
Pankratov Y
影响因子：
64.5
作者：
BEACH, ME;HAWKINS, RD;MAYFORD, M
通讯作者：
MAYFORD, M
影响因子：
5.6
作者：
Ménard C;Quirion R
通讯作者：
Quirion R
影响因子：
16.2
作者：
GEIGER, JRP;MELCHER, T;MONYER, H
通讯作者：
MONYER, H
影响因子：
4.8
作者：
Canal, Frederic;Palygin, Oleg;Mueller, Juergen
通讯作者：
Mueller, Juergen