Activity-regulated cytoskeleton-associated protein Arc/Arg3.1 binds to spectrin and associates with nuclear promyelocytic leukemia (PML) bodies
Activity-regulated cytoskeleton-associated protein Arc/Arg3.1 binds to spectrin and associates with nuclear promyelocytic leukemia (PML) bodies
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DOI：
10.1016/j.brainres.2007.03.079
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发表时间：
2007-06-11
期刊：
影响因子：
2.9
通讯作者：
VanDongen, Antonius M. J.
中科院分区：
文献类型：
--
作者：
Bloomer, Wendy A. C.;VanDongen, Hendrika M. A.;VanDongen, Antonius M. J.
活性调节细胞骨架相关蛋白(Arc/Arg3.1)是一种即刻早期基因，其在中枢神经系统的表达是由突触活动的特定模式诱导的。ARC是长时程增强(LTP)和记忆巩固的晚期所必需的，并与AMPA受体运输有关。由于Arc的分子功能仍不完全清楚，我们已经确定了它在培养的海马神经元和HEK 293T细胞中的亚细胞定位。荧光显微镜实验表明，内源性和外源性Arc蛋白都主要存在于细胞核中，集中在与早幼粒细胞白血病(PML)小体相关的点状区域，这些可能是转录调控的部位。ARC与βIV血影蛋白剪接变异体βSpiv Sigma 5共定位并相互作用，βSpv Sigma 5是与PML小体和核基质相关的核血影蛋白亚型。含有卷曲线圈结构域的一小部分Arc也被限制在β-血影蛋白阳性的斑点上，而分离的血影蛋白同源结构域则广泛定位。最后，Arc和beta Spiv Sigma 5协同增加了PML小体的数量。这些结果表明，Arc作为一种光谱结合蛋白发挥作用，形成一个复合体，可能在细胞核内的转录调控部位发挥作用。(C)2007年，爱思唯尔出版。
Activity-regulated cytoskeleton-associ ated protein (Arc/Arg3.1) is an immediate early gene, whose expression in the central nervous system is induced by specific patterns of synaptic activity. Arc is required for the late-phase of long-term potentiation (LTP) and memory consolidation, and has been implicated in AMPA receptor trafficking. Since Arc's molecular function remains incompletely understood, we have determined its subcellular localization in cultured hippocampal neurons and HEK 293T cells. Fluorescence microscopy experiments revealed that both endogenous and exogenous Arc protein was primarily found in the nucleus, where it concentrated in puncta associated with promyelocytic leukemia (PML) bodies, proposed sites of transcriptional regulation. Arc co-localized and interacted with the beta IV spectrin splice variant beta SpIV Sigma 5, a nuclear spectrin isoform associated with PML bodies and the nuclear matrix. A small region of Arc containing the coiled-coil domain is also restricted to beta-spectrin-positive puncta, while the isolated spectrin homology domain is diffusely localized. Finally, Arc and beta SpIV Sigma 5 synergistically increased the number of PML bodies. These results suggest that Arc functions as a spectrinbinding protein, forming a complex that may provide a role at sites of transcriptional regulation within the nucleus. (c) 2007 Published by Elsevier B.V.