A dual role for the RhoGEF Ephexin5 in regulation of dendritic spine outgrowth.
A dual role for the RhoGEF Ephexin5 in regulation of dendritic spine outgrowth.
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DOI：
10.1016/j.mcn.2017.02.001
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发表时间：
2017-04
期刊：
影响因子：
--
通讯作者：
Zito K
中科院分区：
文献类型：
--
作者：
Hamilton AM;Lambert JT;Parajuli LK;Vivas O;Park DK;Stein IS;Jahncke JN;Greenberg ME;Margolis SS;Zito K
新树突棘的生长与新突触的形成密切相关，并且被认为是支持学习的经验依赖性回路可塑性的重要组成部分。在这里，我们研究了RhoGEF Ephexin 5在驱动活动依赖性脊柱生长中的作用。我们发现，降低Ephexin 5水平增加了脊柱生长，而增加Ephexin 5水平以GEF依赖性方式降低了脊柱生长，表明Ephexin 5作为脊柱生长的抑制剂。值得注意的是，我们发现增加的神经活动导致神经元树突中Ephexin 5水平的蛋白酶体依赖性降低，这可以促进在增加的神经活动后观察到的增强的脊柱生长。令人惊讶的是，我们还发现在新的棘长出之前，在未来新棘的位点处的树突上Ephexin 5-GFP水平升高。此外，降低神经元Ephexin 5水平抑制新的脊柱生长在响应于神经活动和树突的局部神经元能刺激的全球增加，这表明Ephexin 5是必要的活动依赖性脊柱生长。我们的数据支持一个模型，其中Ephexin 5在脊柱发生中起双重作用，既作为整体脊柱生长的制动器，又作为新脊柱的位点特异性形成的必要组成部分。
The outgrowth of new dendritic spines is closely linked to the formation of new synapses, and is thought to be a vital component of the experience-dependent circuit plasticity that supports learning. Here, we examined the role of the RhoGEF Ephexin5 in driving activity-dependent spine outgrowth. We found that reducing Ephexin5 levels increased spine outgrowth, and increasing Ephexin5 levels decreased spine outgrowth in a GEF-dependent manner, suggesting that Ephexin5 acts as an inhibitor of spine outgrowth. Notably, we found that increased neural activity led to a proteasome-dependent reduction in the levels of Ephexin5 in neuronal dendrites, which could facilitate the enhanced spine outgrowth observed following increased neural activity. Surprisingly, we also found that Ephexin5-GFP levels were elevated on the dendrite at sites of future new spines, prior to new spine outgrowth. Moreover, lowering neuronal Ephexin5 levels inhibited new spine outgrowth in response to both global increases in neural activity and local glutamatergic stimulation of the dendrite, suggesting that Ephexin5 is necessary for activity-dependent spine outgrowth. Our data support a model in which Ephexin5 serves a dual role in spinogenesis, acting both as a brake on overall spine outgrowth and as a necessary component in the site-specific formation of new spines.
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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：
3.7
作者：
Kusuhara S;Fukushima Y;Fukuhara S;Jakt LM;Okada M;Shimizu Y;Hata M;Nishida K;Negi A;Hirashima M;Mochizuki N;Nishikawa S;Uemura A
通讯作者：
Uemura A
影响因子：
16.2
作者：
Nishiyama J;Yasuda R
通讯作者：
Yasuda R
影响因子：
64.5
作者：
Dalva, MB;Takasu, MA;Greenberg, ME
通讯作者：
Greenberg, ME
影响因子：
64.8
作者：
Engert, F;Bonhoeffer, T
通讯作者：
Bonhoeffer, T