Wnt Signaling Mediates LTP-Dependent Spine Plasticity and AMPAR Localization through Frizzled-7 Receptors.
Wnt Signaling Mediates LTP-Dependent Spine Plasticity and AMPAR Localization through Frizzled-7 Receptors.
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DOI：
10.1016/j.celrep.2018.03.119
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发表时间：
2018-04-24
期刊：
影响因子：
8.8
通讯作者：
Salinas PC
中科院分区：
文献类型：
--
作者：
McLeod F;Bossio A;Marzo A;Ciani L;Sibilla S;Hannan S;Wilson GA;Palomer E;Smart TG;Gibb A;Salinas PC
突触的结构和功能可塑性对学习和记忆至关重要。长期增强（LTP）诱导促进脊柱生长和AMPAR在兴奋性突触的积累，导致突触强度增加。谷氨酸启动了这些过程，但细胞外调节剂的作用尚未完全确定。wnt是脊柱形成所必需的；然而，它们对活动介导的脊柱可塑性和AMPAR定位的影响尚不清楚。我们发现LTP诱导迅速增加突触Wnt7a/b蛋白水平。内源性wnt的急性阻断或突触后卷曲-7 （Fz7）受体的缺失会损害ltp介导的突触强度、脊柱生长和AMPAR在突触的定位。SEP-GluA1的实时成像和单粒子跟踪显示Wnt7a快速促进突触AMPAR的募集和捕获。Wnt7a通过Fz7诱导camkii依赖性脊柱SynGAP缺失，并通过PKA磷酸化增加突触外AMPARs。我们确定了Wnt-Fz7信号在ltp介导的ampar突触积累和脊柱可塑性中的关键作用。LTP介导的脊柱可塑性和AMPAR运输需要Wnt-Fz7信号，LTP诱导可快速提升脊柱Wnt7a/b蛋白，Wnt7a诱导突触和突触外AMPAR的快速募集，Wnt7a- fz7通过CaMKII、PKA和ERK级联促进突触AMPAR定位。McLeod等人发现，通过激活CaMKII、ERK和PKA通路，Wnt7a- fz7信号是LTP介导的脊柱可塑性、AMPAR定位和突触强度所必需的。他们的研究结果表明，细胞外Wnt蛋白是ltp介导的结构和功能突触可塑性的重要上游启动物。
The structural and functional plasticity of synapses is critical for learning and memory. Long-term potentiation (LTP) induction promotes spine growth and AMPAR accumulation at excitatory synapses, leading to increased synaptic strength. Glutamate initiates these processes, but the contribution from extracellular modulators is not fully established. Wnts are required for spine formation; however, their impact on activity-mediated spine plasticity and AMPAR localization is unknown. We found that LTP induction rapidly increased synaptic Wnt7a/b protein levels. Acute blockade of endogenous Wnts or loss of postsynaptic Frizzled-7 (Fz7) receptors impaired LTP-mediated synaptic strength, spine growth, and AMPAR localization at synapses. Live imaging of SEP-GluA1 and single-particle tracking revealed that Wnt7a rapidly promoted synaptic AMPAR recruitment and trapping. Wnt7a, through Fz7, induced CaMKII-dependent loss of SynGAP from spines and increased extrasynaptic AMPARs by PKA phosphorylation. We identify a critical role for Wnt-Fz7 signaling in LTP-mediated synaptic accumulation of AMPARs and spine plasticity. LTP-mediated spine plasticity and AMPAR trafficking require Wnt-Fz7 signaling LTP induction rapidly elevates Wnt7a/b protein at spines Wnt7a induces the fast recruitment of synaptic and extrasynaptic AMPARs Wnt7a-Fz7 promotes synaptic AMPAR localization via CaMKII, PKA, and ERK cascades McLeod et al. reveal that Wnt7a-Fz7 signaling is required for LTP-mediated spine plasticity, AMPAR localization, and synaptic strength through the activation of the CaMKII, ERK, and PKA pathways. Their findings demonstrate that extracellular Wnt proteins are crucial upstream initiators of LTP-mediated structural and function synaptic plasticity.
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影响因子：
16.6
作者：
Ciani L;Marzo A;Boyle K;Stamatakou E;Lopes DM;Anane D;McLeod F;Rosso SB;Gibb A;Salinas PC
通讯作者：
Salinas PC
DOI：
10.1523/jneurosci.1746-10.2010
发表时间：
2010-09-01
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Fortin DA;Davare MA;Srivastava T;Brady JD;Nygaard S;Derkach VA;Soderling TR
通讯作者：
Soderling TR
影响因子：
16.2
作者：
Ataman, Bulent;Ashley, James;Budnik, Vivian
通讯作者：
Budnik, Vivian
影响因子：
5.7
作者：
Budnik V;Salinas PC
通讯作者：
Salinas PC
影响因子：
64.8
作者：
Harward SC;Hedrick NG;Hall CE;Parra-Bueno P;Milner TA;Pan E;Laviv T;Hempstead BL;Yasuda R;McNamara JO
通讯作者：
McNamara JO