Actin capping protein regulates postsynaptic spine development through CPI-motif interactions.
Actin capping protein regulates postsynaptic spine development through CPI-motif interactions.
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DOI：
10.3389/fnmol.2022.1020949
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发表时间：
2022
影响因子：
4.8
通讯作者：
Zheng, James Q.
中科院分区：
文献类型：
--
作者：
Myers, Kenneth R.;Fan, Yanjie;McConnell, Patrick;Cooper, John A.;Zheng, James Q.
树突棘是富含肌动蛋白的小型突起，对哺乳动物大脑中功能性回路的形成至关重要。在发育过程中，树突棘最初是动态的丝状伪足样突起，随后被含有膨大头部的相对稳定的树突棘所取代。肌动蛋白细胞骨架的重塑在树突棘形态的形成和改变中起关键作用，然而许多潜在的调节机制仍不清楚。封端蛋白（CP）是一种主要的肌动蛋白调节蛋白，它封闭肌动蛋白丝的带刺末端，并促进致密分支肌动蛋白网络的形成。降低CP的表达会损害成熟树突棘的形成，导致丝状伪足样突起数量增加以及突触传递出现缺陷。在此，我们表明CP促进树突突起的稳定，从而导致稳定成熟树突棘的形成。然而，CP在树突棘中的定位和功能需要与含有封端蛋白相互作用（CPI）基序的蛋白质相互作用。我们发现含有CPI基序的蛋白质双丝蛋白 - 1（Twf1）也定位在树突棘上，在CP在树突棘中的富集过程中发挥作用。降低Twf1的表达会导致丝状伪足样突起密度增加以及树突突起稳定性降低，这与降低CP的表达情况类似。最后，我们表明CP直接与Shank相互作用并调节其在树突棘中的积累。这些结果表明，CP在树突棘中的时空调节不仅控制着稳定的突触后树突棘结构形成背后的肌动蛋白动力学，而且在突触功能背后的突触后装置的组装中也起着重要作用。
Dendritic spines are small actin-rich protrusions essential for the formation of functional circuits in the mammalian brain. During development, spines begin as dynamic filopodia-like protrusions that are then replaced by relatively stable spines containing an expanded head. Remodeling of the actin cytoskeleton plays a key role in the formation and modification of spine morphology, however many of the underlying regulatory mechanisms remain unclear. Capping protein (CP) is a major actin regulating protein that caps the barbed ends of actin filaments, and promotes the formation of dense branched actin networks. Knockdown of CP impairs the formation of mature spines, leading to an increase in the number of filopodia-like protrusions and defects in synaptic transmission. Here, we show that CP promotes the stabilization of dendritic protrusions, leading to the formation of stable mature spines. However, the localization and function of CP in dendritic spines requires interactions with proteins containing a capping protein interaction (CPI) motif. We found that the CPI motif-containing protein Twinfilin-1 (Twf1) also localizes to spines where it plays a role in CP spine enrichment. The knockdown of Twf1 leads to an increase in the density of filopodia-like protrusions and a decrease in the stability of dendritic protrusions, similar to CP knockdown. Finally, we show that CP directly interacts with Shank and regulates its spine accumulation. These results suggest that spatiotemporal regulation of CP in spines not only controls the actin dynamics underlying the formation of stable postsynaptic spine structures, but also plays an important role in the assembly of the postsynaptic apparatus underlying synaptic function.
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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：
5.6
作者：
Hilton DM;Aguilar RM;Johnston AB;Goode BL
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影响因子：
7.7
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Johnston AB;Hilton DM;McConnell P;Johnson B;Harris MT;Simone A;Amarasinghe GK;Cooper JA;Goode BL
通讯作者：
Goode BL
影响因子：
11
作者：
Durand CM;Perroy J;Loll F;Perrais D;Fagni L;Bourgeron T;Montcouquiol M;Sans N
通讯作者：
Sans N
影响因子：
4.8
作者：
Hakala, Markku;Kalimeri, Maria;Lappalainen, Pekka
通讯作者：
Lappalainen, Pekka