CASK and CaMKII function in the mushroom body α'/β' neurons during Drosophila memory formation.
CASK and CaMKII function in the mushroom body α'/β' neurons during Drosophila memory formation.
复制标题
DOI：
10.3389/fncir.2013.00052
复制
发表时间：
2013
影响因子：
3.5
通讯作者：
Hodge JJ
中科院分区：
文献类型：
--
作者：
Malik BR;Gillespie JM;Hodge JJ
Ca2+/CaM 丝氨酸/苏氨酸激酶 II (CaMKII) 是突触可塑性和记忆机制中的核心分子。 CaMKII 可塑性的一个重要特征是其在苏氨酸 287 (T287) 处自磷酸化后能够切换到钙 (Ca2+) 独立的组成型活性状态。第二对位点，即钙调蛋白 (CaM) 结合区域中的 T306 T307，一旦自磷酸化，就会阻止随后的 CaM 结合，并在突触可塑性和记忆过程中使激酶失活。最近，一种称为 Ca2+/CaM 依赖性丝氨酸蛋白激酶 (CASK) 的突触分子已被证明可以控制两组 CaMKII 自磷酸化事件，因此有望成为记忆的关键调节因子。我们发现，全长 CASK 或仅删除其 CaMK 样结构域和 L27 结构域会破坏中期记忆 (MTM) 和长期记忆 (LTM)，而蘑菇体神经元 α'/β' 子集中的 CASK 功能是记忆所必需的。同样，直接改变这些神经元中 CaMKII 自磷酸化的水平可以消除 MTM 和 LTM。 CASK 和 CaMKII 自磷酸化的需要不是发育性的，因为仅在成年 α'/β' 神经元中对它们进行操作就足以消除记忆。 α'/β' 神经元中 CASK 或 CaMKII 的过度表达也会阻断 MTM 和 LTM。在CASK突变体的α'/β'神经元中果蝇或人类CASK的过表达完全挽救了记忆，证实α'/β'神经元中的CASK信号对于果蝇记忆形成是必要且充分的，并且CASK的神经元功能在果蝇和人类之间是保守的。在细胞水平上，α'/β'神经元中 CaMKII 的过度表达增加了活性依赖性 Ca2+ 反应，而 CaMKII 的减少则降低了这种反应。同样，减少 CASK 或直接在 α'/β' 中表达磷酸模拟 CaMKII T287D 转基因，同样会减少 Ca2+ 信号传导。我们的结果与 CASK 在记忆形成所需的途径中调节 CaMKII 自磷酸化一致，该途径涉及 α'/β' 神经元中 Ca2+ 信号传导的活动依赖性变化。
Ca2+/CaM serine/threonine kinase II (CaMKII) is a central molecule in mechanisms of synaptic plasticity and memory. A vital feature of CaMKII in plasticity is its ability to switch to a calcium (Ca2+) independent constitutively active state after autophosphorylation at threonine 287 (T287). A second pair of sites, T306 T307 in the calmodulin (CaM) binding region once autophosphorylated, prevent subsequent CaM binding and inactivates the kinase during synaptic plasticity and memory. Recently a synaptic molecule called Ca2+/CaM-dependent serine protein kinase (CASK) has been shown to control both sets of CaMKII autophosphorylation events and hence is well poised to be a key regulator of memory. We show deletion of full length CASK or just its CaMK-like and L27 domains disrupts middle-term memory (MTM) and long-term memory (LTM), with CASK function in the α′/β′ subset of mushroom body neurons being required for memory. Likewise directly changing the levels of CaMKII autophosphorylation in these neurons removed MTM and LTM. The requirement of CASK and CaMKII autophosphorylation was not developmental as their manipulation just in the adult α′/β′ neurons was sufficient to remove memory. Overexpression of CASK or CaMKII in the α′/β′ neurons also occluded MTM and LTM. Overexpression of either Drosophila or human CASK in the α′/β′ neurons of the CASK mutant completely rescued memory, confirming that CASK signaling in α′/β′ neurons is necessary and sufficient for Drosophila memory formation and that the neuronal function of CASK is conserved between Drosophila and human. At the cellular level CaMKII overexpression in the α′/β′ neurons increased activity dependent Ca2+ responses while reduction of CaMKII decreased it. Likewise reducing CASK or directly expressing a phosphomimetic CaMKII T287D transgene in the α′/β′ similarly decreased Ca2+ signaling. Our results are consistent with CASK regulating CaMKII autophosphorylation in a pathway required for memory formation that involves activity dependent changes in Ca2+ signaling in the α′/β′ neurons.
登录
查看更多内容
DOI：
10.1523/jneurosci.1882-10.2010
发表时间：
2010-12-08
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Akalal DB;Yu D;Davis RL
通讯作者：
Davis RL
影响因子：
3.7
作者：
Donelson NC;Kim EZ;Slawson JB;Vecsey CG;Huber R;Griffith LC
通讯作者：
Griffith LC
影响因子：
3.5
作者：
Chen, Kaiyun;Featherstone, David E.
通讯作者：
Featherstone, David E.
影响因子：
64.5
作者：
Ashraf, SI;McLoon, AL;Kunes, S
通讯作者：
Kunes, S
DOI：
10.1016/j.bbrc.2009.03.015
发表时间：
2009-04-24
影响因子：
3.1
作者：
Huang, Tzyy-Nan;Hsueh, Yi-Ping
通讯作者：
Hsueh, Yi-Ping