Overexpression of drebrin A in immature neurons induces the accumulation of F-actin and PSD-95 into dendritic filopodia, and the formation of large abnormal protrusions

Overexpression of drebrin A in immature neurons induces the accumulation of F-actin and PSD-95 into dendritic filopodia, and the formation of large abnormal protrusions
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DOI:
10.1016/j.mcn.2005.06.008
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发表时间:
2005-09-01
影响因子:
3.5
通讯作者:
Shirao, T
Shirao, T
中科院分区:
医学3区
文献类型:
--
作者:
Mizu, T;Takahashi, H;Shirao, T

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Dreplastin A是一种神经元特异性的F-肌动蛋白结合蛋白,在脊柱形成中起着关键作用。本研究利用体外培养的海马神经元,在突触前终末发育不完全的条件下,表达绿色荧光蛋白标记的dreplastin A(GFP-DA)。GFP-DA在树突状突起中积累并形成大的异常结构。由于这些结构在缺乏MAP 2免疫染色方面与丝状伪足相似,我们将它们命名为“megapodia”,意思是大的树突状丝状伪足。F-actin和PSD-95在巨足中也有积累,且其积累量与GFP-DA的积累量显著相关,但GFP-DA的表达并不促进丝状伪足向棘状伪足的形态变化。这些结果表明,drebrin-A通过蛋白质-蛋白质相互作用在丝状伪足中积累了刺驻留蛋白,并表明刺的形成需要drebrin-A表达的增加和功能性突触前接触的同时发生。(c)2005年爱思唯尔公司All rights reserved.
Drebrin A is a neuron-specific F-actin binding protein, and plays a pivotal role in the spine formation. In this study, we expressed drebrin A tagged with green fluorescent protein (GFP-DA) in hippocampal neurons at 7-9 days in vitro when presynaptic terminals are not fully maturated. GFP-DA was accumulated in dendritic protrusions and formed large abnormal structures. Since these structures were similar to filopodia in terms of lack of MAP2 immunostaining, we named them "megapodia" meaning large dendritic filopodia. F-actin and PSD-95 were also accumulated in megapodia, and their amounts were significantly correlated with that of GFP-DA. However, the expression of GFP-DA did not result in the promotion of the morphological change from filopodia into spines. These results demonstrate that drebrin A accumulates spine-resident proteins via protein-protein interaction in filopodia, and suggest that the spine formation requires the concurrence of the increase of drebrin-A expression and the functional presynaptic contact. (c) 2005 Elsevier Inc. All rights reserved.