The CaMKII/NMDAR complex as a molecular memory.
The CaMKII/NMDAR complex as a molecular memory.
复制标题
DOI：
10.1186/1756-6606-6-10
复制
发表时间：
2013-02-14
期刊：
影响因子：
3.6
通讯作者：
Lisman J
中科院分区：
文献类型：
--
作者：
Sanhueza M;Lisman J
CaMKII是一种主要的突触蛋白，在Ca2+通过NMDARs内流诱导长期增强（LTP）时被激活。这种激活是LTP诱导所必需的，但该激酶在LTP维持中的作用尚不清楚。阐明维持机制可能有助于深入了解构成存储记忆稳定性基础的分子过程。在这篇简短的综述中，我们将概述评估LTP维护机制的标准。所评估的具体假设是LTP是由活化的CaMKII与NMDAR的复合物维持的。支持这一假设的证据是充分的，但需要进一步的实验，特别是确定LTP诱导后复合体的时间过程和持久性。还需要进一步的工作来阐明CaMKII/NMDAR复合体如何产生突触的结构生长，这是晚期LTP的基础。Frey和Morris提出，LTP晚期与LTP诱导过程中分子标签的设置有关，该分子标签随后允许激活的突触捕获负责LTP晚期的蛋白质。然而，导致晚期LTP的结构生长的分子过程是完全不清楚的。基于已知的结合反应，我们提出了标签/捕获假说的第一个分子特异性版本：CaMKII/NMDAR复合体一旦形成，就充当标签，然后导致涉及致密蛋白、delta-连环蛋白和n -钙粘蛋白（其中一些是新合成的）的结合级联反应。-连环蛋白结合AMPA结合蛋白（ABP），导致ltp诱导的AMPA通道含量增加。突触后n -钙粘蛋白的加入，以及突触前侧的互补增加，导致突触大小的跨突触协调增加（以及更多的释放位点）。这表明，通过CaMKII/NMDAR复合物和n -钙粘蛋白二聚体的联合作用，突触强度得以稳定储存。这些n -钙粘蛋白对具有冗余存储，可以以类似于DNA碱基配对的方式提供信息稳定性。
CaMKII is a major synaptic protein that is activated during the induction of long-term potentiation (LTP) by the Ca2+ influx through NMDARs. This activation is required for LTP induction, but the role of the kinase in the maintenance of LTP is less clear. Elucidating the mechanisms of maintenance may provide insights into the molecular processes that underlie the stability of stored memories. In this brief review, we will outline the criteria for evaluating an LTP maintenance mechanism. The specific hypothesis evaluated is that LTP is maintained by the complex of activated CaMKII with the NMDAR. The evidence in support of this hypothesis is substantial, but further experiments are required, notably to determine the time course and persistence of complex after LTP induction. Additional work is also required to elucidate how the CaMKII/NMDAR complex produces the structural growth of the synapse that underlies late LTP. It has been proposed by Frey and Morris that late LTP involves the setting of a molecular tag during LTP induction, which subsequently allows the activated synapse to capture the proteins responsible for late LTP. However, the molecular processes by which this leads to the structural growth that underlies late LTP are completely unclear. Based on known binding reactions, we suggest the first molecularly specific version of tag/capture hypothesis: that the CaMKII/NMDAR complex, once formed, serves as a tag, which then leads to a binding cascade involving densin, delta-catenin, and N-cadherin (some of which are newly synthesized). Delta-catenin binds AMPA-binding protein (ABP), leading to the LTP-induced increase in AMPA channel content. The addition of postsynaptic N-cadherin, and the complementary increase on the presynaptic side, leads to a trans-synaptically coordinated increase in synapse size (and more release sites). It is suggested that synaptic strength is stored stably through the combined actions of the CaMKII/NMDAR complex and N-cadherin dimers. These N-cadherin pairs have redundant storage that could provide informational stability in a manner analogous to the base-pairing in DNA.
登录
查看更多内容
影响因子：
2.9
作者：
Feng B;Raghavachari S;Lisman J
通讯作者：
Lisman J
影响因子：
3.5
作者：
Bourne, Jennifer N.;Harris, Kristen M.
通讯作者：
Harris, Kristen M.
影响因子：
9.2
作者：
Israely, I;Costa, RM;Liu, X
通讯作者：
Liu, X
影响因子：
16.2
作者：
Barria, A;Malinow, R
通讯作者：
Malinow, R
DOI：
10.1073/pnas.0710213105
发表时间：
2008-01-08
影响因子：
11.1
作者：
Jiang, Xin;Lautermilch, Nathan J.;Catterall, William A.
通讯作者：
Catterall, William A.