Molecular architecture of synaptic actin cytoskeleton in hippocampal neurons reveals a mechanism of dendritic spine morphogenesis.
Molecular architecture of synaptic actin cytoskeleton in hippocampal neurons reveals a mechanism of dendritic spine morphogenesis.
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DOI：
10.1091/mbc.e09-07-0596
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发表时间：
2010-01-01
影响因子：
3.3
通讯作者：
Svitkina T
中科院分区：
文献类型：
--
作者：
Korobova F;Svitkina T
用铂复制电子显微镜对树突棘及其前体细胞骨架的高分辨结构进行了表征。这些突起的肌动蛋白结构的意想不到的特征极大地改变了现有的细长膜突起的细胞骨架组织模式。大脑中的兴奋性突触在学习和记忆中起着关键作用。突触后蘑菇状结构、树突棘以及可能的突触前终末的形成和功能依赖于肌动蛋白细胞骨架的重塑。然而，突触的细胞骨架结构仍然未知，阻碍了对突触形态发生的理解。利用铂复制电子显微镜，我们研究了树突棘、其前体、树突丝足突和突触前突触的细胞骨架组织和分子组成。包含Arp2/3复合体和帽蛋白的分支肌动蛋白细丝网络是脊柱头和突触前突触的主要特征。令人惊讶的是，脊椎的颈部和底部，以及树突状的丝状足突，也含有一个由分支和线状肌动蛋白细丝组成的网络，该网络对Arp2/3复合体、帽蛋白和肌球蛋白II呈免疫阳性反应，而不是对筋膜蛋白呈阳性反应。因此，细长的丝状突起的结构支撑不需要紧密的肌动蛋白细丝束。动态地，树突丝状足从树突干的密度中出现，在电子显微镜下，树突干中含有与树突微管相关的分支肌动蛋白网络。我们认为，树突棘的形态发生始于伸长到树突状丝状基座的肌动蛋白斑块，其末端随后通过依赖于Arp2/3复合体的成核而扩张，其长度受肌球蛋白II依赖的收缩能力的调节。
The high resolution structure of the cytoskeleton in dendritic spines and their precursors, dendritic filopodia, was characterized by platinum replica electron microscopy. The unexpected features of the actin architecture of these protrusions dramatically change the existing paradigm of cytoskeletal organization of elongated membrane protrusions. Excitatory synapses in the brain play key roles in learning and memory. The formation and functions of postsynaptic mushroom-shaped structures, dendritic spines, and possibly of presynaptic terminals, rely on actin cytoskeleton remodeling. However, the cytoskeletal architecture of synapses remains unknown hindering the understanding of synapse morphogenesis. Using platinum replica electron microscopy, we characterized the cytoskeletal organization and molecular composition of dendritic spines, their precursors, dendritic filopodia, and presynaptic boutons. A branched actin filament network containing Arp2/3 complex and capping protein was a dominant feature of spine heads and presynaptic boutons. Surprisingly, the spine necks and bases, as well as dendritic filopodia, also contained a network, rather than a bundle, of branched and linear actin filaments that was immunopositive for Arp2/3 complex, capping protein, and myosin II, but not fascin. Thus, a tight actin filament bundle is not necessary for structural support of elongated filopodia-like protrusions. Dynamically, dendritic filopodia emerged from densities in the dendritic shaft, which by electron microscopy contained branched actin network associated with dendritic microtubules. We propose that dendritic spine morphogenesis begins from an actin patch elongating into a dendritic filopodium, which tip subsequently expands via Arp2/3 complex-dependent nucleation and which length is modulated by myosin II-dependent contractility.
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影响因子：
3.3
作者：
Racz, B;Weinberg, RJ
通讯作者：
Weinberg, RJ
树突状棘的超微结构：突触和脊柱形态之间的相关性。
影响因子：
4.3
作者：
Arellano JI;Benavides-Piccione R;Defelipe J;Yuste R
通讯作者：
Yuste R
DOI：
10.1083/jcb.200809046
发表时间：
2009-04-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hotulainen P;Llano O;Smirnov S;Tanhuanpää K;Faix J;Rivera C;Lappalainen P
通讯作者：
Lappalainen P
影响因子：
25
作者：
Marrs, GS;Green, SH;Dailey, ME
通讯作者：
Dailey, ME
影响因子：
25
作者：
Ackermann, M;Matus, A
通讯作者：
Matus, A