Fragile X mental retardation protein (FMRP) interacting proteins exhibit different expression patterns during development
Fragile X mental retardation protein (FMRP) interacting proteins exhibit different expression patterns during development
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DOI：
10.1016/j.ijdevneu.2015.02.004
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发表时间：
2015-05-01
影响因子：
1.8
通讯作者：
Catania, M. V.
中科院分区：
文献类型：
--
作者：
Bonaccorso, C. M.;Spatuzza, M.;Catania, M. V.
脆性X综合征是由脆性X智力低下蛋白（FMRP）表达缺乏引起的，FMRP是一种参与mRNA转运和翻译的RNA结合蛋白。FMRP是mRNA核糖核蛋白复合物的一个组成部分，它可以直接或间接地与一系列蛋白质相互作用，分别通过双杂交选择和免疫共沉淀证明。大多数与FMRP相互作用的蛋白是RNA结合蛋白，如FXR 1 P、FXR 2 P和82-FIP。有趣的是，FMRP也可以直接与细胞质蛋白CYFIP 1和CYFIP 2相互作用，这些蛋白不结合RNA，并将FMRP与RhoGT 3途径连接起来。与这些不同蛋白的相互作用可能通过影响FMRP与RNA的亲和力以及通过影响FMRP通过Rho/Rac GTP酶重塑细胞骨架的能力来调节FMRP的功能。为了更好地确定FMRP及其相互作用蛋白在脑发育过程中的关系，我们分析了FMRP及其相互作用蛋白在不同年龄的野生型（WT）小鼠皮质、纹状体、海马和小脑中的表达模式。FMRP和FXR 2 P在第一周强烈表达，此后逐渐下降，在小脑中比在皮质中表达更快。FXR 1 P也在早期表达，并在发育后期表现出减少，在这两个区域具有相似的发育模式。CYFIP 1在所有年龄段都有表达，在出生后第三周达到峰值。相反，CYFIP 2和82-FIP（仅在前脑区域）在P3时中度表达，并在P7后逐渐增加。在一般情况下，每种蛋白质的表达模式是相似的，除了82-FIP，它表现出强表达在P3和低水平，在小脑发育后期的区域。我们的数据表明，FMRP及其相互作用的蛋白质有不同的发展模式的表达，并建议FMRP可能优先与某些蛋白质在早期和晚期的发展阶段。特别是，FMRP的RNA结合和细胞骨架重塑功能可能在发育过程中受到不同的调节。(C)2015爱思唯尔有限公司版权所有。
Fragile X syndrome is caused by the lack of expression of fragile X mental retardation protein (FMRP), an RNA-binding protein involved in mRNA transport and translation. FMRP is a component of mRNA ribonucleoprotein complexes and it can interact with a range of proteins either directly or indirectly, as demonstrated by two-hybrid selection and co-immunoprecipitation, respectively. Most of FMRP-interacting proteins are RNA-binding proteins such as FXR1P, FXR2P and 82-FIP. Interestingly, FMRP can also interact directly with the cytoplasmic proteins CYFIP1 and CYFIP2, which do not bind RNA and link FMRP to the RhoGTPase pathway. The interaction with these different proteins may modulate the functions of FMRP by influencing its affinity to RNA and by affecting the FMRP ability of cytoskeleton remodeling through Rho/Rac GTPases. To better define the relationship of FMRP with its interacting proteins during brain development, we have analyzed the expression pattern of FMRP and its interacting proteins in the cortex, striatum, hippocampus and cerebellum at different ages in wild type (WT) mice. FMRP and FXR2P were strongly expressed during the first week and gradually decreased thereafter, more rapidly in the cerebellum than in the cortex. FXR1P was also expressed early and showed a reduction at later stages of development with a similar developmental pattern in these two regions. CYFIP1 was expressed at all ages and peaked in the third post-natal week. In contrast, CYFIP2 and 82-FIP (only in forebrain regions) were moderately expressed at P3 and gradually increased after P7. In general, the expression pattern of each protein was similar in the regions examined, except for 82-FIP, which exhibited a strong expression at P3 and low levels at later developmental stages in the cerebellum. Our data indicate that FMRP and its interacting proteins have distinct developmental patterns of expression and suggest that FMRP may be preferentially associated to certain proteins in early and late developmental periods. In particular, the RNA-binding and cytoskeleton remodeling functions of FMRP may be differently modulated during development. (C) 2015 Elsevier Ltd. All rights reserved.